bluuebunny/crossref_metadata_2025 huggingface dataset:
Reactive Tabu Search in a Team-Learning Problem
Authors: Shen Yuelin
Published: May 2008

In designing an MBA core curriculum, student cohorts are assigned to a number of sections in each term. In a given term, different sections have exclusive schedules, while the cohorts in the same section have an identical schedule. By altering the cohorts in the sections through the terms, any cohort can meet as many other cohorts as possible via the core courses. We model this problem as a quadratic integer programming problem and construct the performance measure to characterize the properties of the problem. We design a reactive tabu search metaheuristic that solves the model effectively. Two other solution methods, constraint logic programming and an improved hill-climbing search heuristic, are also discussed. We analyze the computational results for the cases in practice.
Pooling and Dynamic Forgetting Effects in Multitheme Advertising: Tracking the Advertising Sales Relationship with Particle Filters
Authors: Bruce Norris I.
Published: May 2008

Firms often use a pool or series of advertising themes in their campaigns. Thus, for example, a firm may employ some of its advertising to promote price-related themes or messages and other of its advertising to promote product-related themes. This study examines the interdependence that can occur between pairs of themes in a pool (i.e., pooling effects), the impact of these pooling effects on the allocation of advertising expenditures, and the factors that can affect forgetting rates (or, conversely, carry-over rates) in a multitheme advertising environment. The study measures pooling, wear out, and forgetting (carry-over) effects for a campaign that uses five different advertising themes. To obtain these measures, I extend the linear Nerlove-Arrow (NA) (1962) model to a nonlinear model of advertising theme quality and goodwill and estimate the extended model using Markov chain Monte Carlo (MCMC) and particle filtering ideas. Particle filtering belongs to a class of sequential Monte Carlo (SMC) methods designed to estimate nonlinear/nonnormal state space models. Results show that forgetting (or carry-over) rates may be time varying and a function of prior goodwill (past advertising) and other advertising variables. Results show, moreover, that pooling effects can reduce theme wear out and, in turn, significantly improve advertising efficiency.
Distribution Coordination Between Suppliers and Customers with a Consolidation Center
Authors: Song Haiqing , Hsu Vernon N. , Cheung Raymond K.
Published: May 2008

We study a problem faced by a third-party logistics provider (3PL) who needs to coordinate shipments between suppliers and customers through a consolidation center in a distribution network. Products from a supplier have one release time and are consolidated into a single shipment to the consolidation center. At the center, products to the same destination are also consolidated into a single shipment, and the consolidation time can be as early as possible or as late as possible, depending on the customer requirement and cost structure. The 3PL needs to determine the pickup times from the suppliers, delivery times to the customers, and the transportation options while considering product release times, latest arrival times, different consolidation policies, and the transportation and storage costs involved. In this paper, we formulate this problem as a nonlinear optimization problem, show it is an NP-hard problem, and develop a dual-based solution method for the general problem. Utilizing the problem's special structure, we show that the Lagrangian dual of the general problem can be solved optimally as a linear program, thus allowing us to accelerate the computation of a lower bound to the optimal objective function value. The experimental results show that the dual-based algorithm provides solutions with objective function values, which are on average within 3.24% of optimality. We also consider a version of the problem where each customer orders products from all suppliers, for which we develop a polynomial-time algorithm.
Per-Seat, On-Demand Air Transportation Part II: Parallel Local Search
Authors: Espinoza D. , Garcia R. , Goycoolea M. , Nemhauser G. L. , Savelsbergh M. W. P.
Published: May 2008

The availability of relatively cheap small jet aircrafts suggests a new air transportation business: dial-a-flight, an on-demand service in which travelers call a few days in advance to schedule transportation. A successful on-demand air transportation service requires an effective scheduling system to construct minimum-cost pilot and jet itineraries for a set of accepted transportation requests. In Part I, we introduced an integer multicommodity network flow model with side constraints for the dial-a-flight problem and showed that small instances can be solved effectively. Here, we demonstrate that high-quality solutions for large-scale real-life instances can be produced efficiently by embedding the core optimization technology in a local search scheme. To achieve the desired level of performance, metrics were devised to select neighborhoods intelligently, a variety of search diversification techniques were included, and an asynchronous parallel implementation was developed.
Aquaporin-4 in Acute Cerebral Edema Produced by Clostridium perfringens Type D Epsilon Toxin
Authors: Finnie J. W. , Manavis J. , Blumbergs P. C.
Published: May 2008

Sheep, particularly lambs, with high circulating levels of Clostridium perfringens type D epsilon toxin develop severe neurologic signs and often die suddenly. On microscopic examination, in the brain, there is microvascular endothelial injury and diffuse vasogenic edema. The aquaporin (AQP) family of membrane water-channel proteins, especially AQP-4, is important in the regulation of water balance in the brain and facilitates reabsorption of excess fluid. In rats given epsilon toxin, generalized cerebral edema was demonstrated by marked albumin extravasation and was correlated with widespread upregulation of AQP-4 in astrocytes. These results suggest that AQP-4 has a role in the clearance of edema fluid from brains damaged by this clostridial toxin.
Experimental Reproduction of Severe Bluetongue in Sheep
Authors: Maclachlan N. J. , Crafford J. E. , Vernau W. , Gardner I. A. , Goddard A. , Guthrie A. J. , Venter E. H.
Published: May 2008

Sheep inoculated with a virulent South African strain of bluetongue (BT) virus serotype 4 developed severe clinical signs and lesions characteristic of fulminant BT, including coronitis, hemorrhage and ulceration of the mucosal lining of the oral cavity and forestomaches, hemorrhage in the wall of the pulmonary artery, and focally extensive necrosis of skeletal muscle, especially of the neck. At necropsy, up to 14 days after infection, the infected sheep exhibited striking pulmonary edema, edema of the subcutaneous tissues and fascial planes of the head and neck, and pleural and pericardial effusion of varying severity. A reliable model for experimental reproduction of fulminant BT in sheep will facilitate future studies to better characterize the pathogenesis of this disease, particularly as it regards the mechanisms responsible for the increased vascular permeability that characterizes BT and related orbiviral diseases such as African horse sickness.
Regional Pulmonary Veno-occlusion: A Newly Identified Lesion of Equine Exercise-induced Pulmonary Hemorrhage
Authors: Williams K. J. , Derksen F. J. , de Feijter-Rupp H. , Pannirselvam R. R. , Steel C. M. , Robinson N. E.
Published: May 2008

Exercise-induced pulmonary hemorrhage (EIPH) is common in horses following intense exertion, occurring in up to 75% of racing Thoroughbreds and Standardbreds. In spite of this, the pathogenesis of EIPH is poorly understood. In 7 racing Thoroughbred horses with EIPH, 6 sections were collected from the left and right lung, representing the cranial, middle, and caudal region of the dorsal and ventral lung (84 sites total). Grossly, both right and left lungs had numerous dark brown to blue-black foci along the caudodorsal visceral pleura. Tissue sections were stained with hematoxylineosin, Masson's trichrome, and Prussian blue. Verhoeff Van Gieson and immunohistochemistry for α-smooth muscle actin were used to assess the pulmonary vasculature. Histologic scores (HS = 0–3) were assigned to each region/slide for the presence and severity of 5 findings: interstitial fibrosis, hemosiderin accumulation, pleural/interlobular septal thickness, arterial and venous wall thickness, and evidence of angiogenesis (maximum cumulative HS = 15). Thirty-nine of the 84 (46%) sections were histologically normal (HS = 0); 33/84 (39%) were mildly to moderately affected, with small amounts of hemosiderin and fibrosis (HS = 1–9) while 12/84 (14%), primarily from the dorsocaudal lung, had severe vascular remodeling, fibrosis, and hemosiderin accumulation (HS = 10–15). In the latter, veno-occlusive remodeling of the intralobular veins colocalized with hemosiderosis, fibrosis, hypertrophy of vessels within the pleura, and interlobular septa and bronchial neovascularization. We propose that regional veno-occlusive remodeling, especially within the caudodorsal lung fields, contributes to the pathogenesis of EIPH, with the venous remodeling leading to regional vascular congestion and hemorrhage, hemosiderin accumulation, fibrosis, and bronchial angiogenesis.
An Outbreak of Fatal Herpesvirus Infection in Domestic Rabbits in Alaska
Authors: Jin L. , Valentine B. A. , Baker R. J. , Löhr C. V. , Gerlach R. F. , Bildfell R. J. , Moerdyk-Schauwecker M.
Published: May 2008

A herpesvirus infection affecting mini Rex and crossbred meat rabbits was identified in a rabbitry in Alaska. Illness affected over half of the 55 rabbits on the premises, and 16 rabbits died or were euthanatized because of illness. Disease affected all ages from adults to nursing young and occurred over an approximately 2-month period. Clinical signs included conjunctivitis and periocular swelling, ulcerative dermatitis, progressive weakness, anorexia, respiratory distress, and abortion. Hemorrhagic dermatitis and panniculitis were associated with epidermal microvesicular degeneration, dermal and subcutaneous vascular necrosis, and thrombosis. Eosinophilic intranuclear inclusions consistent with herpesvirus were found within the epidermis and superficial follicular epithelium and within mesenchymal cells within the dermis and subcutis. Syncytial cells containing viral inclusions occurred within the epidermal and superficial follicular epithelium. Other findings were hemorrhagic necrosis of the myocardium with rare intranuclear inclusions within stromal cells, multifocal pulmonary hemorrhage, hemorrhage with sinus erythrophagocytosis in lymph nodes, and massive necrosis and fibrin deposition within red pulp of the spleen. A virus isolated from the skin produced syncytia, intranuclear inclusions, and cell lysis typical of herpesvirus in rabbit kidney cells in vitro. The viral isolate was characterized ultrastructurally as an enveloped virus with icosahedral nucleocapsids 100 nm diameter, consistent with a herpesvirus.
Non-gestational Malignant Placental Site Trophoblastic Tumor of the Ovary in a 4-Year-Old Rhesus Monkey
Authors: Marbaix E. , Defrère S. , Duc K. Ho Minh , Lousse J.-C. , Dehoux J.-P.
Published: May 2008

We report a case of ovarian malignant intermediate-type trophoblastic tumor in a clinically normal, nonpregnant 4-year-old rhesus monkey ( Macaca, mulatta). A large solid lobulated mass replaced the right ovary and filled the pelvis. Multiple metastases were observed within the lungs and the liver. The tumor was histologically identified as predominantly composed of intermediate trophoblastic cells, without prominent hemorrhages and the classic bilaminar pattern of cyto- and syncytiotrophoblastic cells characteristic of choriocarcinoma. Immunohistochemical analysis showed the presence of placental lactogen hormone in many tumor cells and chorionic gonadotropin in a few multinucleated cells consistent with syncytiotrophoblastic differentiation. No other germ cell differentiation was identified in the pelvis mass nor in the metastases. In the absence of previous and present pregnancy, this neoplasm has to be considered as a nongestational malignant placental site trophoblastic tumor of the ovary.
Ovarian Mucinous Cystadenoma with Smooth Muscle Proliferation in a Cynomolgus Monkey (Macaca fascicularis)
Authors: Sato J. , Kokoshima H. , Tsuchitani M.
Published: May 2008

An ovarian mucinous cystadenoma was found in a 5-year-old female cynomolgus monkey ( Macaca fascicularis). The tumor was composed of various sizes of multilocular cystic glands lined by a single layer of mucin-filled epithelium. Each of these cystic glands was surrounded by a large amount of solid fibrous stroma resembling smooth muscle. The ovarian surface epithelium showed partial invagination into the ovarian cortex, and a transition was observed between the surface epithelium and the mucinous cyst-forming epithelium. Immunohistochemically, the stromal cells were positive for α-smooth muscle actin and proliferating cell nuclear antigen. Ultrastructurally, the glandular epithelium had numerous mucinous secretory granules and microvilli. The stromal cells had numerous parallel microfibrils with focal density. It is rare to encounter evidence of a transition from the surface epithelium to the mucinous tumor epithelium and to show stromal smooth muscle proliferation in a mucinous cystadenoma.
Surveillance of the Fracture Behavior of Zircaloy-4 Welds Using the Small Punch Test
Authors: Wei T. , Carr D. G. , Li H. , Smith K. , Harrison R. P.
Published: May 2008

Zircaloy-4 (Zr-4) is a zirconium alloy that has been used extensively within the nuclear industry in both power generation and research reactors. The potential for welded reactor core components to undergo embrittlement during neutron irradiation is an important materials property issue to be considered throughout the service life of the reactor. Of particular interest is the performance of welded joints which depend on the properties of both the weld heat-affected zone (HAZ) and the parent metal. For this work Zr-4 HAZ was simulated using a Gleeble weld simulator to rapidly bring the material into the β-Zr zone at peak temperatures of 1200 and 1400°C. The small punch (SP) test was then used to investigate the variation in fracture behavior of these narrow zones of the weld and compare them with the parent metal. A finite element analysis (FEA) model of the SP test was developed which can be used to predict the deformation and fracture behavior of Zr-4 welds and is compared with the experimental data obtained.
Measurement of Physical Environmental Parameters and Apparent Ventilation Rates Aboard Passenger Aircraft
Authors: Murphy Michael J.
Published: May 2008

As part of the ASHRAE RP-1262 Phase 1 study of the airliner cabin environment, measurements were made of physical environmental parameters aboard four passenger aircraft in revenue service. The objectives of these measurements were to measure physical environmental parameters and ventilation rates on board commercial airliners in revenue service and to correlate those measurements with self-reported health effects and complaints. The measurements included temperature, relative humidity, total pressure, air velocity, sound level, light level, and motion. These measurements were recorded each second throughout the flight. In addition, measurements of carbon dioxide levels in the cabin were made that, along with passenger loadings and assumed metabolic rates, allowed the calculation of an apparent air change rate. Because as another part of the study, passengers filled-out written surveys on their comfort and health experience, this study provides unique simultaneous measurement of both physical environmental parameters in an aircraft cabin and the human response. Results of these measurements are presented as temporal graphs for the duration of the flight and are compared to various benchmarks. Among the results, air change rates ranged from 10 to 16 air changes per hour, noise levels varied from 68 to 80 dBA, according to the location in the cabin. Relative humidity values declined from 30 to 35 % during the boarding process to as low as 7 to 8 % during the cruise portion of the flights. The temperature variation was greatest during the boarding process and was generally near 25°C, during the cruise portion of the flights. Over all four flights, the cabin pressure varied from 562 to 740 torr. There was a wide variation in light levels: from over 8000 lux if sunlight was present, to about 250 lux if the window shades were in use.
The post partum period and the onset of Graves' disease: an overestimated risk factor
Authors: Rotondi Mario , Pirali Barbara , Lodigiani Sara , Bray Simona , Leporati Paola , Chytiris Spyridon , Balzano Simona , Magri Flavia , Chiovato Luca
Published: May 2008

Objective

Aggravation of autoimmune diseases due to a rebound reaction to the pregnancy-associated immune changes is common during the post partum (PP) period. Previous studies demonstrated that up to 45% of women developing Graves' disease (GD) in the childbearing age had a PP onset of disease. Thus, the PP period was identified as a major risk factor for GD onset.

Design

The aim of this study was to evaluate the role of the PP period as a risk factor for GD occurrence.

Methods

The reproductive histories of 291 consecutive GD patients (165 patients in the childbearing age and 126 in the non-childbearing age) were retrospectively collected.

Results

The rate of PP onset of GD in all patients with at least one successful pregnancy was 9.8 and 20.0% when only patients in the childbearing age were considered. In the entire cohort of GD women, independent of their age and parity status (i.e., the number of successful pregnancies), the rate of PP onset of GD was 7.2%. The relative frequencies of the rate of PP onset of GD were similar in relation with increasing parity. The rates of false negative (nulliparous) and false positive (parous non-childbearing+childbearing with a non-PP onset of GD) were estimated. The positive predictive value of the PP period for the onset of GD was less than 10%.

Conclusions

The results of the current study would not support a role for the PP period as a major risk factor for de novo occurrence of GD.
Acrosomal status and mitochondrial activity of human spermatozoa vitrified with sucrose
Authors: Isachenko E , Isachenko V , Weiss J M , Kreienberg R , Katkov I I , Schulz M , Lulat A G-M I , Risopatrón M J , Sánchez R
Published: May 2008

This study investigates the ability of sucrose to protect spermatozoa against mitochondrial damage, artificial cryoinduction of capacitation, and acrosome reaction. Spermatozoa were isolated using the swim-up procedure performed using three different media: (a) human tubal fluid (HTF, control) medium; (b) HTF with 1% human serum albumin (HSA); and (c) HTF with 1% HSA and 0.25 M sucrose. From each group, 30 μl suspensions of cells were dropped directly into liquid nitrogen and stored for at least 24 h. Cells were thawed by quickly submerging the spheres in HTF with 1% HSA at 37 °C with gentle agitation. Sperm motility, viability, mitochondrial membrane potential integrity, spontaneous capacitation, and acrosome reaction were investigated. Sperm viability, acrosome reaction, and capacitation were detected using the double fluorescence chlortetracycline-Hoechst 33258 staining technique. Mitochondrial function was evaluated using a unique fluorescent cationic dye, 5,5′,6,6′-tetrachloro-1-1′,3,3′-tetraethyl-benzamidazolocarbocyanin iodide, commonly known as JC-1. The number of progressively motile spermatozoa was significantly higher in the sucrose-supplemented medium group (57.1±3.2%, P<0.05) when compared with controls (19.4±1.9%). The combination of HSA and sucrose (65.2±2.6%) has a stronger cryoprotective effect on the integrity of mitochondrial membrane potential (P<0.05) compared with HSA alone (32.6±4.7%). In conclusion, vitrification of human spermatozoa with non-permeable cryoprotectants such as HSA and sucrose can effectively cryopreserve the cells without significant loss of important physiological parameters.
Selective estrogen receptor α activation disrupts sex organ differentiation and induces expression of vitellogenin II and very low-density apolipoprotein II in Japanese quail embryos
Authors: Mattsson Anna , Olsson Jan A , Brunström Björn
Published: May 2008

The Japanese quail (Coturnix japonica) is a widely used model species for studying the roles of steroid hormones in avian sex differentiation. The aim of the present study was to elucidate the significance of estrogen receptors α and β (ERα and ERβ) in normal sex differentiation of the reproductive organs in the Japanese quail and in xenoestrogen-induced disruption of reproductive organ differentiation. Real-time PCR indicated that ERα (ESR1) mRNA is expressed in both right and left gonads and Müllerian ducts (MDs) in both sexes during early morphological differentiation. ERβ (ESR2) transcripts were also detected in gonads and MDs, but at very low levels. Both receptor subtypes were expressed in the liver and may therefore mediate the expression of estrogen-regulated egg-yolk proteins. Aromatase mRNA was expressed at much higher levels in female than male gonads as early as embryonic day 5, indicating early sex differences in estrogen synthesis. Treatment with the ERα-selective agonist propyl pyrazole triol showed that frequently reported xenoestrogen effects, such as ovotestis formation, abnormal MD development, and hepatic expression of egg-yolk proteins, were induced by selective activation of ERα. Taken together, our results suggest that activation of ERα is crucial for estrogen-dependent sex differentiation of the reproductive organs and that ERα mediates xenoestrogen-induced toxicity during reproductive development in birds.
Biliary complications following orthotopic liver transplantation. The Hungarian experience
Authors: Nemes Balázs , Zádori Gergely , Hartmann Erika , Németh Andrea , Fehérvári Imre , Görög Dénes , Máthé Zoltán , Dávid Andrea , Jakab Katalin , Sárváry Enikő , Piros László , Tóth Szabolcs , Fazakas János , Gerlei Zsuzsa , Járay Jenő , Doros Attila
Published: May 2008

A szerzők összefoglalják a magyar májátültetési program epeúti szövődményeinek jellemzőit. Feltárják az epeúti szövődmények előfordulási gyakoriságát. Elemzik az epeúti szövődmények típusait és azok megoszlását, valamint hatásukat a beteg-, illetve graftvesztésre. Elemzik az irodalomban már ismert rizikófaktorokat a hazai betegpopulációban. Ismertetik az epeúti szövődmények kezelési lehetőségeit. Retrospektív vizsgálat során a betegeket két csoportba osztották aszerint, hogy a májátültetés után kialakult-e epeúti szövődmény, vagy nem, majd a két csoportot összehasonlították számos vizsgált paraméter, valamint a túlélések szempontjából. Az epeúti szövődményes betegeket tovább csoportosították annak alapján, hogy a szövődmény a májátültetés után három hónapon belül vagy később alakult ki. Ezt a két csoportot szintén összehasonlították a fentebb említett kontrollcsoporttal. Egyvariációs összehasonlítások esetén a folytonos adatokat a populáció homogenitásának vizsgálata után (Levene-teszt) kétmintás
t
-próbával, illetve Mann–Whitney-féle U-teszttel, a kategorikus adatokat χ
2
-próbával, illetve Kaplan–Meier-analízissel vizsgálták. A túlélést Kaplan–Meier-metodikával vizsgálták. Az eredményeket valamennyi statisztikai próbánál akkor tekintették szignifikánsnak, ha a
p
< 0,05 volt.
Eredmények:
Epeúti szövődmény a betegek 26%-ában jelent meg, 290 vizsgált beteg közül 76 esetben. A leggyakoribb a szűkület (18%), majd az epecsorgás (9%), a necrosis (6%), végül az ischaemiás típusú epeúti károsodás (3%). Epeúti szövődmények esetén az 5 éves kumulatív túlélés rosszabb (55%), mint ezek hiányában (66%), és a retranszplantációk aránya is magasabb (15%) volt. A leggyakoribb kezelési típusok: intervenciós radiológiai (69%), sebészi (17%), ERCP (14%).
Következtetések:
Az epeúti szövődmények aránya megfelel a nemzetközi közléseknek, 2002 óta arányuk csökkent. Epeúti szövődmények kialakulásának rizikófaktorai: cholangitis, az arteria hepatica thrombosisa és stenosisa, magas bevitt intraoperatív volumen, valamint az akut rejectio. Korai epeúti szövődmények gyakran társultak a beültetett májgraft kezdeti gyenge működésével (ún. „initial poor function”). A korai epeúti szövődmények felelősek a túlélés csökkenéséért, a késői szövődmények inkább az életminőséget rontják. Az epeúti szövődményes betegeket döntően intervenciós radiológiai módszerekkel kezelték.
Calcium Handling in Human Embryonic Stem Cell-Derived Cardiomyocytes
Authors: Satin Jonathan , Itzhaki Ilanit , Rapoport Sophia , Schroder Elizabeth A. , Izu Leighton , Arbel Gil , Beyar Rafael , Balke C. William , Schiller Jackie , Gepstein Lior
Published: May 2008

The objective of the current study was to characterize calcium handling in developing human embryonic stem cell-derived cardiomyocytes (hESC-CMs). To this end, real-time polymerase chain reaction (PCR), immunocytochemistry, whole-cell voltage-clamp, and simultaneous patch-clamp/laser scanning confocal calcium imaging and surface membrane labeling with di-8-aminonaphthylethenylpridinium were used. Immunostaining studies in the hESC-CMs demonstrated the presence of the sarcoplasmic reticulum (SR) calcium release channels, ryanodine receptor-2, and inositol-1,4,5-trisphosphate (IP3) receptors. Store calcium function was manifested as action-potential-induced calcium transients. Time-to-target plots showed that these action-potential-initiated calcium transients traverse the width of the cell via a propagated wave of intracellular store calcium release. The hESC-CMs also exhibited local calcium events (“sparks”) that were localized to the surface membrane. The presence of caffeine-sensitive intracellular calcium stores was manifested following application of focal, temporally limited puffs of caffeine in three different age groups: early-stage (with the initiation of beating), intermediate-stage (10 days post-beating [dpb]), and late-stage (30–40 dpb) hESC-CMs. Calcium store load gradually increased during in vitro maturation. Similarly, ryanodine application decreased the amplitude of the spontaneous calcium transients. Interestingly, the expression and function of an IP3-releasable calcium pool was also demonstrated in the hESC-CMs in experiments using caged-IP3 photolysis and antagonist application (2 μM 2-Aminoethoxydiphenyl borate). In summary, our study establishes the presence of a functional SR calcium store in early-stage hESC-CMs and shows a unique pattern of calcium handling in these cells. This study also stresses the importance of the functional characterization of hESC-CMs both for developmental studies and for the development of future myocardial cell replacement strategies.

Disclosure of potential conflicts of interest is found at the end of this article.
Lentiviral Vector Gene Transfer Is Limited by the Proteasome at Postentry Steps in Various Types of Stem Cells
Authors: Santoni de Sio Francesca Romana , Gritti Angela , Cascio Paolo , Neri Margherita , Sampaolesi Maurilio , Galli Cesare , Luban Jeremy , Naldini Luigi
Published: May 2008

The isolation of human embryonic and somatic stem cells of different types has made it possible to design novel gene and cell replacement therapies. Vectors derived from retro/lentiviruses are used to stably introduce genes into stem cells and their progeny. However, the permissivity to retroviral infection varies among cell types. We previously showed that hematopoietic stem cells are poorly permissive to human immunodeficiency virus (HIV)-derived vectors and that pharmacological inhibition of the proteasome strongly enhances gene transfer. Here we report that the proteasome limits lentiviral gene transfer in all stem cell types tested, including embryonic, mesenchymal, and neural, of both human and mouse origin. Remarkably, this inhibitory activity was sharply reduced upon differentiation of the stem cells, suggesting that it represents a novel feature of the stem cell/immature progenitor phenotype. Proteasome-mediated inhibition was specific for lentiviral vectors and occurred at a postentry infection step. It was not mediated by activation of nuclear factor-κB, a major signaling pathway modulated by the proteasome, and did not correlate with high proteasome activity. Interaction of the virion core with cyclophilin A was required to maximize the effect of proteasome inhibitor on the infection pathway. These findings are relevant to uncover new mediators of HIV gene transfer and help in designing more effective protocols for the genetic modification of stem cells.

Disclosure of potential conflicts of interest is found at the end of this article.
The Lineage−c-Kit+Sca-1+ Cell Response toEscherichia coliBacteremia in Balb/c Mice
Authors: Zhang Ping , Nelson Steve , Bagby Gregory J. , Siggins Robert , Shellito Judd E. , Welsh David A.
Published: May 2008

During bacterial infection, the bone marrow hematopoietic activity shifts toward granulocyte production, which is critical for host defenses. Along with this enhancement of granulopoiesis, the bone marrow also increases its release of hematopoietic precursors. At the present time, little is known about the commitment of hematopoietic precursor cells, including hematopoietic stem cells and progenitors, in this response. To investigate the hematopoietic precursor cell response to bacterial infection, bacteremia was established in Balb/c mice by i.v. injection of Escherichia coli. Bacteremia caused a 10-fold increase in the number of lineage (lin)−c-kit+Sca-1+ cells in the bone marrow. This dramatic expansion of the lin−c-kit+Sca-1+ cell pool resulted from both increased mitosis of these cells and inversion from lin−c-kit+Sca-1− cell phenotype. Lipopolysaccharide, tumor necrosis factor-α, and interleukin-6 were potent factors capable of mediating phenotypic inversion of lin−c-kit+Sca-1− cells. Cells in the expanded lin−c-kit+Sca-1+ cell pool contained more colony-forming unit-granulocyte/macrophage. Mobilization of lin−c-kit+Sca-1+ cells into the circulation was significantly enhanced following bacteremia. These results demonstrate that the lin−c-kit+Sca-1+ cell population in the bone marrow constitutes a key component of the host defense response to bacteremia. Functional modifications of these primitive hematopoietic precursors are critical for enhancing granulocyte production following bacterial infection.

Disclosure of potential conflicts of interest is found at the end of this article.
Breathing: A Sign of Life and a Unique Area for Reflection and Action
Authors: Ekerholt Kirsten , Bergland Astrid
Published: May 2008

Background and Purpose

The aim of this study was to clarify patients’ experiences of breathing during therapeutic processes in Norwegian psychomotor physical therapy (NPMP).

Subjects and Methods

A qualitative approach was used based on interviews with 9 women and 1 man aged between 41 and 65 years. The data were analyzed with the aid of grounded theory.

Results

Three categories were identified from the participants’ experiences: (1) “Breathing: An Incomprehensible and Disparate Phenomenon,” (2) “Breathing: Access to Meaning and Understanding,” and (3) “Breathing: Enhancing Feelings of Mastery.” Initially, breathing difficulties and bodily pains were described as physical reactions that seemed utterly incomprehensible to the participants. Communication, both verbal and nonverbal, between the patient and the physical therapist was described as vitally important, as was conscious attention to occurrences during the treatment sessions. The participants learned to recognize changes in their breathing patterns, and they became familiar with new bodily sensations. Consequently, they acquired new understanding of these sensations. The feeling and understanding of being an entity (ie, “body and soul”) emerged during therapy. The participants increased their understanding of the interaction between breathing and internal and external influences on their well-being. Their feelings of mastery over their daily lives were enhanced. The therapeutic dialogues gave them the chance to explore, reflect, and become empowered.

Discussion and Conclusion

In experiencing their own breathing, the participants were able to access and identify the muscular and emotional patterns that, linked to particular thoughts and beliefs, had become their characteristic styles of relating to themselves and the world.
The "Going" of the Third Reich: Recivilizing Germans through Political Education
Authors: Buse Dieter K.
Published: May 2008

Historians and political sciences have begun to discuss how and when postwar Germany overcame its authoritarian past and reestablished democracy and a tolerant civil society. This article argues that the national and regional Offices for Political Education have contributed significantly to the recivilizing process. The article provides the first preliminary academic attempt to outline the offices' historical background, their changing institutional structure, and their place in the civic education context since the mid 1950s. A series of case studies examine the historical literature disseminated by specific offices to illustrate the process of overcoming a problematic past and constructing new identities. In turn, the historical role models promoted by the offices, the manner in which federalism was presented, the timing of and fashion in which the Holocaust became a significant theme and the way in which regional identities were understood and fostered, are examined. These cases illustrate how historical information was employed, at first in fairly simple and propagandistic fashion, but always to inculcate democratic and civil norms. The question of the impact of the offices' work is left open, since research on reception has yet to be undertaken, but some evidence about their important contributions to reshaping German values is provided.
The trade‐off between flood‐ and shade‐tolerance: A mortality episode in Carpinus caroliniana in a floodplain forest, Texas
Authors: Mann Lisa E. , Harcombe Paul A. , Elsik I. Sandra , Hall Rosine B.W.
Published: May 2008

Question:

Is a rapid decline in abundance of a dominant species in a bottomland hardwood forest evidence for a trade‐off between flood‐ and shade‐tolerance?

Location:

Bottomland hardwood forest in east Texas, USA.

Methods:

We used 23 years of data on marked individuals to examine abundance, mortality, recruitment and growth of trees before and after a long growing season flood.

Results:

A decline of 47% in abundance and 49% in basal area of Carpinus caroliniana (Betulaceae) occurred between 1989 and 1994 in a bottomland hardwood forest following a long summer flood. Other major species showed little change in abundance or basal area. The Carpinus decline was greater at low elevations suggesting the importance of flooding. Carpinus is rated among the least flood‐tolerant species in the system. It differs from other species of similar flood tolerance in adult stature (midstory) and shade tolerance (tolerant).

Conclusions:

The trade‐off between flood tolerance and shade tolerance can influence dynamics of floodplain forests.
Launching the Trustworthy and Responsible AI Network (TRAIN)
Authors: Embí Peter J. , Rhew David C. , Peterson Eric D. , Pencina Michael. J.
Published: February 2025

This Viewpoint lays out the genesis of Trustworthy and Responsible AI Network (TRAIN) and strategies for ensuring effective and safe use of AI throughout the US health care system.
Moving Toward Implementation of Responsible Artificial Intelligence in Health Care
Authors: van Genderen Michel E. , Kant Ilse M. J. , Tacchetti Carlo , Jovinge Stefan
Published: February 2025

This Viewpoint discusses the Trustworthy and Responsible AI Network Europe (TRAIN-Europe) consortium, an effort of medical and AI experts to oversee, develop, and share ethical practices through collaboration and technological solutions designed to implement responsible AI practices.
White‐Matter Structural Connectivity and Alzheimer's Disease: A Mendelian Randomization Study
Authors: Liu Siyu , Geng Daoying
Published: February 2025

Background

Alzheimer's disease (AD) and white‐matter structural connectivity have been linked in some observational studies, although it is unknown if this is a causal relationship. The purpose of this study was to examine the impact of various white‐matter structural connectivity on AD via a two‐sample multivariate Mendelian randomization (MR) approach.

Methods

The genome‐wide association study (GWAS) of Wainberg et al. provided the summary data on white‐matter structural connectivity, and Bellenguez et al.’s study provided the GWAS aggregated data for AD. MR methods included inverse variance weighted, Mendelian randomization Egger, simple mode, weighted median, and weighted mode. Heterogeneity, horizontal pleiotropy, and “leave‐one‐out” analysis guaranteed the robustness of causation. Finally, reverse MR analysis was conducted on the white‐matter structural connectivity that showed positive results in the forward MR analysis.

Results

Among 206 white‐matter structural connections, we identified 10 connections were strongly correlated with genetic susceptibility to AD. Right‐hemisphere limbic network to thalamus white‐matter structural connectivity and Right‐hemisphere salience_ventral attention network to accumbens white‐matter structural connectivity were positively correlated with the likelihood of AD, while the remaining 8 white‐matter structural connections were negatively related with AD. None of the above 10 white‐matter structural connections have a reverse causal relationship with AD.

Conclusion

Our MR study reveals a certain degree of association between white‐matter structural connectivity and AD, which may provide support for future diagnosis and treatment of AD.
Channel Estimation Based Intelligent Reflecting Surfaces for Massive MIMO System Considering Spatially Correlated Channels
Authors: Amadid Jamal , Khabba Asma , El Ouadi Zakaria , Zeroual Abdelouhab
Published: February 2025

Recently, many fundamental technologies have emerged to boost and improve the performance of existing and future wireless communication systems, one of these technologies being the utilization of intelligent reflecting surfaces (IRS). This work investigates the channel estimation and spectral efficiency (SE) of a Massive multiple‐input multiple‐output (M‐MIMO) system based on an IRS for spatially correlated channels. The system's performance is evaluated in terms of both channel estimation and SE, utilizing the minimum mean square error (MMSE) estimator. Accordingly, a three‐stage M‐MIMO channel estimation assisted by an IRS using the pilot sequences in a more practical propagation environment, that is, spatially correlated channels, wherein the IRS components empower the BS to estimate the uplink reflected channel state information (CSI) (i.e., estimation of reflected channels). In addition, the three stages channel estimate based on pilot sequences is computed and evaluated using the MMSE estimator and the normalized‐mean square error (NMSE) metric, respectively. In this framework, this work proposes a local multiple scattering (LMS) model that describes the spatial correlation (SC) over the proposed uniform rectangular array (URA) by relying on the LMS model that describes the SC over a ULA configuration. In other words, using the Kronecker product (KP) of the correlation matrix constructed through a ULA, we built the correlation matrix that describes the SC over the proposed URA. In contrast to the linear array, the proposed array design is more constrained, leading to a higher degree of SC and better channel estimation quality. Numerical results are provided to assert and validate both our theoretical expression, as well as, the effectiveness of the proposed configuration.
No‐Shows in a Tertiary Care Pediatric Otolaryngology Clinic: Predictors and Impact on Provider Productivity
Authors: Sunkara Yukta , Ulualp Seckin O. , Robinson Kimberly , Lenes‐Voit Felicity , Liu Christopher C. , Mitchell Ron B.
Published: February 2025

Objectives

No‐show appointments (NS) lead to a mismatch between supply and expected demand, operational inefficiency, decreased access to care, and economic deficit. We evaluated the predictors and impact of NS on provider productivity in a tertiary pediatric otolaryngology clinic.

Methods

Patients who had a pediatric otolaryngology clinic appointment were identified. Demographics, type of appointment and clinic visit, provider, insurance, appointment lead time, time of the appointment, caregiver income, distance to the clinic, and season of the year were analyzed. Predictors of NS and loss of providers' work‐RVUs and revenue were assessed. NS and non‐NS populations were compared using χ2 test for categorical variables and Mann–Whitney test for continuous variables. Multivariable analysis was performed with a binary logistics regression model for the prediction of NS.

Results

Of 24,593 appointments, 10,392 (42%) were female, (age median = 5 years) and of the 4627 NS 2016 (44%) were female, (age median = 5 years). Logistic regression identified male (OR: 0.093, 95% CI [0.88–0.99], p = 0.04), Black/African American race (OR: 1.97, 95% CI [1.72–2.26], p < 0.001), spring (OR: 0.88, 95% CI [0.80–0.97], p = 0.007), summer (OR: 0.90, 95% CI [0.83–0.99], p = 0.04), clinic focus‐general clinic (OR: 1.32, 95% CI [1.20–1.45], p < 0.001), and appointment lead times of 0–7 days (OR: 0.36, 95% CI [0.29–0.46], p < 0.001), 8–14 days (OR: 0.49, 95% CI [0.39–0.63], p < 0.001), 15–30 days (OR: 0.60, 95% CI [0.47–0.76], p < 0.001) were predictive of NS. The estimated loss of work‐RVU ranged from 3852 to 14,820, and the estimated loss of revenue ranged from $276,831 to $959,908 per year.

Conclusions

No‐show appointments led to a substantial loss of provider productivity and revenue. Of the multiple demographic and clinic visit determinants associated with high NS rates, appointment lead time can be tested in future studies of strategies to reduce NS.

Level of Evidence

4
U-NET-based deep learning for automated detection of lathe checks in homogeneous wood veneers
Authors: Marc Caroline , Marcon Bertrand , Denaud Louis , Girardon Stéphane
Published: February 2025

Automated detection of lathe checks in wood veneers presents significant challenges due to their variability and the natural properties of wood. This study explores the use of two convolutional neural networks (U-Net architecture) to enhance the precision and efficiency of lathe checks detection in poplar veneers. The approach involves sequential application of two U-Nets: the first for detecting lathe checks through semantic segmentation, and the second for refining these predictions by connecting fragmented lathe checks. Post-processing techniques are applied to denoise the mappings and extract precise lathe check characteristics. The first U-Net demonstrated strong performance in predicting lathe check presence, with precision and recall scores of 0.822 and 0.835, respectively. The second U-Net refined predictions by linking disjointed segments, improving the overall lathe checks mapping process. Comparative analysis with manual methods revealed comparable or superior performance of the automated approach, especially for shallow lathe checks. The results highlight the potential of the proposed method for efficient and reliable lathe check detection in wood veneers.
Digital design and manufacturing of a railway bogie demonstrator via multi-material wire arc directed energy deposition
Authors: Queguineur Antoine , Daareyni Amirmohammad , Mokhtarian Hossein , Isakov Matti , Rook Remco , Ya Wei , Goulas Constantinos , Hascoët Jean-Yves , Ituarte Iñigo Flores
Published: February 2025

The sequential digital design and manufacturing of components play a crucial role in realizing the industrial potential of directed energy deposition (DED), particularly when employing an electric arc as the energy source to melt a filler wire (DED-ARC). This study explores the application of DED-ARC for manufacturing large-scale, load-bearing structures, using a railway bogie as a case study. Originally a cast Bettendorf-type design, the bogie was redesigned using a multi-material approach. High-strength low-alloy (HSLA) steel was utilized in high-stress areas, while low-carbon steel was used elsewhere to reduce mass, enhance manufacturability, and improve repairability. The workflow included computer-aided design (CAD), topological optimization, finite element analysis (FEA), material selection, and iterative CAD modifications to address process constraints. The redesigned bogie underwent pre-manufacturing, fabrication, and a final scan of the as-built part. Representative multi-material wall samples were characterized, revealing typical microstructures and elastic limits of 468 MPa and 737 MPa for ER70S-6 and ER100S-G, respectively. These tensile properties were incorporated into FEA verification simulations, demonstrating a higher safety factor compared to the original design. A CAD-to-part analysis, including scan comparisons, highlighted manufacturing-induced deformation, material-dependent over-thickness, and localized geometric variations. This study offers a comprehensive overview of the DED-ARC process, from design through characterization, and demonstrates its capability to produce high-quality industrial components. The findings underscore the manufacturability and potential of DED-ARC for fabricating robust, multi-material structures for demanding applications.
Influence of real-world cue exposure and mood states on drinking: testing neurobiological models of alcohol use disorder
Authors: Meredith Lindsay R. , BaskervilleMann Wave-Ananda , Lee Carrie , Grodin Erica N. , Wassum Kate M. , Ray Lara A.
Published: February 2025

Rationale

Two prominent neurobiological models of addiction, the allostatic and incentive-sensitization models, have guided clinical research on alcohol use disorder (AUD). While these models are often viewed in isolation, it is plausible these theories are complimentary.

Objectives

Use naturalistic, daily diary reports to determine whether positive and negative mood states influence alcohol cue sensitivity in a clinical sample with AUD.

Methods

This is an exploratory analysis of daily diary data collected from a non-treatment seeking sample with current AUD over two weeks. Eligible adult participants (N = 50) were enrolled in a medication trial for AUD. Each morning, participants retrospectively reported on pre-drinking mood states, alcohol cue exposure, and craving levels, and subsequent alcohol intake occurring the previous day. Multilevel models tested the singular and interactive relationships between cue exposure and mood states with craving and drinking. Within-person and between-person outcomes were assessed. Exploratory analyses examined whether individuals with withdrawal-related dysphoria were more vulnerable to mood states and cue-reactivity.

Results

Greater cue exposure was associated with higher daily drinking levels (p = .001), but not daily alcohol craving. Higher negative mood (p < .0001) and lower positive mood (p = .012) were associated with higher daily alcohol craving, but not same-day drinking. As negative mood levels increased (p < .01) and positive mood levels decreased (p = .010), the relationship between cue exposure and same-day drinking became stronger. These findings were most pronounced among those with withdrawal-related dysphoria.

Conclusions

Findings provided concomitant support for the allostatic model and incentive-sensitization model as determinants of alcohol craving and drinking among individuals with AUD.