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Although bone morphogenetic proteins (BMPs) initially showed effective induction of ectopic bone growth in muscle, it has since been determined that these proteins, as members of the TGF-β superfamily, play a diverse and critical array of biological roles. These roles include regulating skeletal and bone formation, angiogenesis, and development and homeostasis of multiple organ systems. Disruptions of the members of the TGF-β/BMP superfamily result in severe skeletal and extra-skeletal irregularities, suggesting high therapeutic potential from understanding this family of BMP proteins. Although it was once one of the least characterized BMPs, BMP9 has revealed itself to have the highest osteogenic potential across numerous experiments both in vitro and in vivo, with recent studies suggesting that the exceptional potency of BMP9 may result from unique signaling pathways that differentiate it from other BMPs. The effectiveness of BMP9 in inducing bone formation was recently revealed in promising experiments that demonstrated efficacy in the repair of critical sized cranial defects as well as compatibility with bone-inducing bio-implants, revealing the great translational promise of BMP9. Furthermore, emerging evidence indicates that, besides its osteogenic activity, BMP9 exerts a broad range of biological functions, including stem cell differentiation, angiogenesis, neurogenesis, tumorigenesis, and metabolism. This review aims to summarize our current understanding of BMP9 across biology and the body.

Objective: Ambulatory surgical centers (ASC’s) have emerged as an alternative to the traditional hospital- based outpatient department (HOPD). We aim to determine the effect of surgical setting on ...

The purpose of this study is to evaluate the influence of intra-articular corticosteroid injections prior to knee arthroscopy on the rate of postoperative infection and define a safe timing interval between intra-articular corticosteroid injections and subsequent knee arthroscopy. The PearlDiver Database was used to identify patients who underwent a knee arthroscopy from 2007 to 2017. Patients were sorted into an injection cohort if they received any intra-articular corticosteroid injections within 6 months before surgery and a control cohort if they received no such injections. The injection cohort was then stratified into subgroups based on the timing of the most recent injection. We identified two types of postoperative infection in the 6 months following surgery: a broad definition of infection using knee infection diagnoses, and a narrow definition of infection requiring surgical treatment. The effects of the timing of preoperative corticosteroid injections on the rates of postoperative infection were investigated. The rate of broadly defined postoperative infection was significantly higher in the 0 to 2 weeks injection group (6.90%, 20/290) than the control group (2.01%, 1,449/72,089, p

Notch is a cell–cell signaling pathway that is involved in a host of activities including development, oncogenesis, skeletal homeostasis, and much more. More specifically, recent research has demonstrated the importance of Notch signaling in osteogenic differentiation, bone healing, and in the development of the skeleton. The craniofacial skeleton is complex and understanding its development has remained an important focus in biology. In this review we briefly summarize what recent research has revealed about Notch signaling and the current understanding of how the skeleton, skull, and face develop. We then discuss the crucial role that Notch plays in both craniofacial development and the skeletal system, and what importance it may play in the future.

Cartilage injuries caused by arthritis or trauma pose formidable challenges for effective clinical management due to the limited intrinsic proliferative capability of chondrocytes. Autologous stem cell-based therapies and transgene-enhanced cartilage tissue engineering may open new avenues for the treatment of cartilage injuries. Bone morphogenetic protein 2 (BMP2) induces effective chondrogenesis of mesenchymal stem cells (MSCs) and can thus be explored as a potential therapeutic agent for cartilage defect repair. However, BMP2 also induces robust endochondral ossification. Although the precise mechanisms through which BMP2 governs the divergence of chondrogenesis and osteogenesis remain to be fully understood, blocking endochondral ossification during BMP2-induced cartilage formation may have practical significance for cartilage tissue engineering. Here, we investigate the role of Sox9-donwregulated Smad7 in BMP2-induced chondrogenic differentiation of MSCs. We find that overexpression of Sox9 leads to a decrease in BMP2-induced Smad7 expression in MSCs. Sox9 inhibits BMP2-induced expression of osteopontin while enhancing the expression of chondrogenic marker Col2a1 in MSCs. Forced expression of Sox9 in MSCs promotes BMP2-induced chondrogenesis and suppresses BMP2-induced endochondral ossification. Constitutive Smad7 expression inhibits BMP2-induced chondrogenesis in stem cell implantation assay. Mouse limb explant assay reveals that Sox9 expands BMP2-stimulated chondrocyte proliferating zone while Smad7 promotes BMP2-intitated hypertrophic zone of the growth plate. Cell cycle analysis indicates that Smad7 induces significant early apoptosis in BMP2-stimulated MSCs. Taken together, our results strongly suggest that Sox9 may facilitate BMP2-induced chondrogenesis by downregulating Smad7, which can be exploited for effective cartilage tissue engineering.

Decaps are the panacea for the noise-related issues. Due to the short distance advantage, decaps are embedded in the fan-out wafer-level package instead of the printed circuit board. These decaps, generally thicker than chips, will have a crucial influence on the molding process as well. A lot of issues are encountered in the molding process, especially with lots of decaps, i.e., voids issues, incomplete filling issues, and die shift issues. In an optimized design, all these issues should be prevented or reduced as much as possible. In this paper, design flow for the wafer-level molding process is demonstrated and design guidelines are provided. Three important evaluation standards are used to evaluate the design, i.e., incomplete filling, drag force, and voids. Two kinds of design parameters, structure parameters (i.e., die placement, die size and thickness, and so on) and process parameters (i.e., vacuum pressure, filling speed, and so on), are optimized in the whole study. Optimization of these parameters helps the real wafer-level molding process to be conducted smoothly.

With rapid advances in understanding molecular pathogenesis of human diseases in the era of genome sciences and systems biology, it is anticipated that increasing numbers of therapeutic genes or targets will become available for targeted therapies. Despite numerous setbacks, efficacious gene and/or cell-based therapies still hold the great promise to revolutionize the clinical management of human diseases. It is wildly recognized that poor gene delivery is the limiting factor for most in vivo gene therapies. There has been a long-lasting interest in using viral vectors, especially adenoviral vectors, to deliver therapeutic genes for the past two decades. Among all currently available viral vectors, adenovirus is the most efficient gene delivery system in a broad range of cell and tissue types. The applications of adenoviral vectors in gene delivery have greatly increased in number and efficiency since their initial development. In fact, among over 2,000 gene therapy clinical trials approved worldwide since 1989, a significant portion of the trials have utilized adenoviral vectors. This review aims to provide a comprehensive overview on the characteristics of adenoviral vectors, including adenoviral biology, approaches to engineering adenoviral vectors, and their applications in clinical and pre-clinical studies with an emphasis in the areas of cancer treatment, vaccination and regenerative medicine. Current challenges and future directions regarding the use of adenoviral vectors are also discussed. It is expected that the continued improvements in adenoviral vectors should provide great opportunities for cell and gene therapies to live up to its enormous potential in personalized medicine.

Shannon's fundamental bound for perfect secrecy says that the source entropy cannot be larger than the entropy of the secret key initially shared by the sender and the legitimate receiver. Massey gave an information theoretic proof of this result, and his proof does not require independence of the key and the source message. By further assuming independence, some stronger results, which govern the probability distributions of the key and the ciphertext, can be shown. These results illustrate that the key entropy is not less than the logarithm of the message sample size in any cipher achieving perfect secrecy, even if the source distribution is fixed. The same bound also applies to the entropy of the ciphertext. These results still hold if the source message has been compressed before encryption.

Die shift issues that arise in embedded wafer-level packaging because of the mold flow process is investigated in this paper, along with solution strategies to address them. The nonlinearity trend of the die shift in the experimental inspection is explained and captured by the numerical simulation with a consideration of the coefficient of thermal expansion effect coupled with the mold flow effect. Optimizing the initial diameter of molding compounds, increasing the thickness of molding compounds, and reducing the filling speed are the three solutions we demonstrate for reducing the drag force. Die shift generated by the mold flow could be reduced by optimizing these controllable parameters.

Hybrid speciation represents a relatively rapid form of diversification. Early models of homoploid hybrid speciation suggested that reproductive isolation between the hybrid species and progenitors primarily resulted from karyotypic differences between the species. However, genic incompatibilities and ecological divergence may also be responsible for isolation. Iris nelsonii is an example of a homoploid hybrid species that is likely isolated from its progenitors primarily by strong prezygotic isolation, including habitat divergence, floral isolation and post-pollination prezygotic barriers. Here, we used linkage mapping and quantitative trait locus (QTL) mapping approaches to investigate genomic collinearity and the genetic architecture of floral differences between I. nelsonii and one of its progenitor species I. hexagona. The linkage map produced from this cross is highly collinear with another linkage map produced between I. fulva and I. brevicaulis (the two other species shown to have contributed to the genomic makeup of I. nelsonii), suggesting that karyotypic differences do not contribute substantially to isolation in this homoploid hybrid species. Similar to other studies of the genetic architecture of floral characteristics, at least one QTL was found that explained >20% variance in each color trait, while minor QTLs were detected for each morphological trait. These QTLs will serve as hypotheses for regions under selection by pollinators.

Tendinopathy is a common and debilitating condition that results in significant deficits in performance and prolonged time away from activity. For this reason, much effort has been placed in defining beneficial and cost-effective treatments. This review has outlined the current literature on some of the most widely used therapies for cases of tendinopathy. As such, recommendations remain limited by the evidence available. The variability in both quantity and quality of research into tendinopathy treatments makes it difficult to make definitive treatment recommendations. In general, however, a reasonable first line of treatment for tendinopathy should include a course of NSAIDs and eccentric exercise-based physical therapy. Corticosteroid injections seem to offer excellent short-term pain relief but lack long term efficacy. Alternative injections, such as PRP, have shown short-term efficacy for tendinopathy sufferers; data are lacking to support sclerosing agents and proteinase inhibitors. Operative management seems to offer some benefit in symptomatic relief but carries a higher complication rate than other treatment options and should be reserved only for patients recalcitrant to other more conservative options. Although the inability to make definitive therapeutic recommendations in some instances is discouraging, it is important to note that a lack of high-quality evidence supporting specific treatments does not necessarily imply that they are inherently ineffective. Given the growing prevalence of tendinopathy and the impact it has on the general public, it is more important now than ever to continue the search for the most effective and accessible treatment modalities.

OBJECTIVES To conduct a randomised controlled trial to evaluate the short-term clinical and radiographic efficacy of the NobelActive™ system and to evaluate the relative importance of achieving primary stability at placement. MATERIALS AND METHODS A total of 32 subjects were recruited and, using a split-mouth design, the NobelActive(TM) implant was compared with a contralaterally matched Branemark implant. Both implants were placed in a single surgical procedure into healed sites using a one-stage protocol and reviewed at monthly intervals. NobelActive(TM) implants were functionally loaded with provisional restorations at 1 month and all implants were restored with final crowns 3 months post-implant placement. The implant was assessed using peak insertion torque values, resonance frequency analysis (RFA), clinical parameters, digital subtraction radiography, and cone beam computed tomography. RESULTS The insertion torque was significantly greater for the NobelActive(TM) implant group (P = 0.02), although no observable difference in RFA values were found. Preliminary results of 6 months follow-up suggest comparable clinical and radiographic healing responses between the test and control implants. Within the limits of the sample population, the survival rates were lower with the test implants, although this difference was not statistically significant. CONCLUSIONS The NobelActive(TM) implant system requires higher insertion torques and can also achieve greater primary stability compared with a control implant system. Short-term survival and marginal bone levels of NobelActive(TM) and control implants are comparable, although the NobelActive(TM) implant system appeared to be more technique-sensitive.

The phylogenetically-conserved vertebrate transcription factor, NFIB, is an orchestrator of glial differentiation in the developing mammalian central nervous system. We found NFIB expression to be reduced in glioblastoma (GBM), the commonest and most lethal primary adult brain cancer, so investigated what effect increased expression of NFIB had on GBM. Increased expression of NFIB in primary GBM cell lines induced expression of markers of glial differentiation, inhibited cell proliferation, reduced stem/progenitor cell growth, altered cell cycle progression and inhibited tumor growth in murine models of GBM. We thus identified NFIB to be a novel tumor suppressor gene in GBM.

RADA16‐I is a synthetic type I self‐assembling peptide nanofiber scaffold (SAPNS) which may serve as a novel biocompatible hemostatic agent. Its application in neurosurgical hemostasis, however, has not been explored. Although RADA16‐I is nontoxic and nonimmunogenic, its intrinsic acidity may potentially provoke inflammation in the surgically injured brain. We conducted an animal study to compare RADA16‐I with fibrin sealant, a commonly used agent, with the hypothesis that the former would be a comparable alternative. Using a standardized surgical brain injury model, 30 Sprague–Dawley rats were randomized into three treatment groups: RADA16‐I, fibrin sealant or gelatin sponge (control). Animals were sacrificed on day 3 and 42. Astrocytic and microglial infiltrations within the cerebral parenchyma adjacent to the operative site were significantly lower in the RADA16‐I and fibrin sealant groups than control. RADA16‐I did not cause more cellular inflammatory response despite its acidity when compared with fibrin sealant. Immunohistochemical studies showed infiltration by astrocytes and microglia into the fibrin sealant and RADA16‐I grafts, suggesting their potential uses as tissue scaffolds. RADA16‐I is a promising candidate for further translational and clinical studies that focus on its applications as a safe and effective hemostat, proregenerative nanofiber scaffold as well as drug and cell carrier.

In this paper, the fabrication process and results of 2.5D through silicon interposer (TSI) package using polymer based RDL and chip-on-wafer (CoW) stacking-first approach is presented. The through silicon interposer is fabricated on a 300 mm silicon substrate with Cu filled vias of aspect ratio of 1:10. Fine-pitch Cu RDL using semi-additive process and polymer based dielectric is used to form the 3 layer of rerouting layer on front-side. Chips with micro-bumps are flip chip assembled onto the under bump metallization (UBM) of the 12 inch interposer substrate using thermal compression bonding via chip-on-wafer (CoW) format on the thick interposer substrate A wafer level molding process is used to form the over-mold encapulation over the assembled chips. The over-mold encapsulation is mechanically thinned down to reduce the warpage of the molded interposer and temporary bonded to a silicon carrier. Mechanical-grinding and chemical mechanical polishing (CMP) is used to expose the Cu vias from the backside. Cu-RDL process is used to form the backside re-routing layer and UBM for solder bumps. The completed interposer wafer is then diced into singulated packages for assembled to printed circuit board (PCB).

The fluorescence properties of poly(2,6-(4-phenylquinoline)) (PPQ) and poly(ethylene glycol)-b-poly(p-phenylene ethynylene)-b-poly(ethylene glycol) (triblock) within porous glass were investigated. Emission was shifted to different wavelengths by varying the pore size. The emission shift is attributed to the unique aggregation state at each pore size. At small pore sizes (∼8 nm), the polymers emit lights as the monomer-like states (490 nm for PPQ and 420 nm for triblock when excited at 365 nm). The emission shifts to the red region as the pore size increases until it reaches 30 nm at which PPQ emits light at 545 nm and triblock at 500 nm. As the pore size continues to increase, there is sufficient space for the relatively smaller PPQ to orient in different directions, reducing the interchain interaction and causing the emission to be blue-shifted to ∼500 nm. The bulky triblock, however, prevents the polymer from orienting randomly, obliging the chains to align in a relatively planar geometry and retaining...

Background: Ischaemic nephropathy is currently a major public health issue in atherosclerotic populations. Although atherosclerotic cardiovascular disease in Asia has reached epidemic proportions over the last two decades, there is little published data on the prevalence of atherosclerotic renal artery stenosis (ARAS) in Oriental subjects. Because ARAS may be clinically silent until end-stage renal failure sets in, it is important to identify patients with significant but clinically unsuspected ARAS. ARAS and coronary artery disease (CAD) often coexist. Aims: The purpose of the present study was to evaluate the prevalence and predictors of ARAS among Chinese patients with CAD. Methods: A total of 230 consecutive Chinese patients with CAD confirmed by coronary angiography underwent an abdominal aortogram in the same sitting to screen for ARAS. Patient demographics and comorbid­ities were analysed for any association with ARAS. Results: A total of 34 (14.8%) patients was found to have significant ARAS. Age and multivessel CAD were independent predictors of ARAS. Hypertension, renal insufficiency, extracranial cerebrovascular disease and female gender were also associated with a higher risk of ARAS but did not independently predict ARAS. Conclusion: Clinically silent yet angiographically significant ARAS is common among CAD patients. The prevalence and predictors of ARAS among Chinese patients with CAD are similar to those reported for Caucasian subjects. Underlying ARAS should be suspected in CAD patients with such comorbidities as hypertension, renal insufficiency, extracranial cerebrovascular disease, and more so in the elderly and those with multivessel disease. (Intern Med J 2003; 33: 280−285)

Background:Although platelet-rich plasma (PRP) is used clinically to augment tendon healing, bone morphogenetic protein–13 (BMP13) may provide a better therapeutic avenue to improve early tendon healing and repair.Hypothesis:Exogenous expression of BMP13 in tenocytes will up-regulate genes involved in tendon healing. Direct delivery of adenovirus-mediated BMP13 (AdBMP13) into the injured rat supraspinatus tendon will increase biomechanical properties.Study Design:Controlled laboratory study.Methods:Exogenous expression of BMP13 and the major growth factors in PRP (transforming growth factor–β1 [TGF-β1], vascular endothelial growth factor–A [VEGF-A], and platelet-derived growth factor–BB [PDGF-BB]) was accomplished by using recombinant adenoviral vectors. The expression of tendon- and matrix-associated genes in growth factor–treated tenocytes was analyzed by use of semiquantitative reverse-transcription polymerase chain reaction. A total of 32 rats with supraspinatus defect were divided into 4 groups and injected with adenovirus-containing green fluorescent protein (AdGFP; negative control), PRP, AdBMP13, or PRP+AdBMP13. All rats were sacrificed at 2 weeks after surgery, and tendons were harvested for biomechanical testing and histologic analysis.Results:BMP13 up-regulated type III collagen expression compared with AdGFP control and PRP growth factors ( P < .01). BMP13 and PRP growth factors each up-regulated fibronectin expression ( P < .01). There was an increase in stress to failure in each of the 3 treatment groups ( P < .05 for PRP; P < .01 for AdBMP13 or PRP+AdBMP13) compared with AdGFP control. AdBMP13 demonstrated higher stress to failure than did the PRPs ( P < .01). The addition of PRP did not increase the BMP13-enhanced stress to failure or stiffness. The biomechanical results were further supported by histologic analysis of the retrieved samples.Conclusion:Exogenous expression of BMP13 enhances tendon healing more effectively than PRP as assessed by tendon- and matrix-associated gene expression, biomechanical testing, and histologic analysis.Clinical Relevance:While PRP is used in the clinical setting, BMP13 may be explored as a superior biofactor to improve rotator cuff tendon healing and reduce the incidence of retears.

Intratumoural hypoxia is associated with chemoresistance in glioblastoma multiforme (GBM), a highly malignant brain tumour. Adaptive response to endoplasmic reticulum stress induced by temozolomide is a major obstacle in recurrent GBM. We investigated whether hyperoxia resensitizes temozolomide-resistant GBM cells to temozolomide by abrogating the hypoxia-induced, unfolded protein response (UPR)-related protective mechanisms.We examined changes to key UPR modulators in temozolomide-sensitive and -resistant human GBM cells (D54 and U87) treated with/without temozolomide at different oxygen concentrations using western blotting, and cytotoxic benefits of overexpressing key chaperone, P4HB, in GBM cells (U87 and U251) under normoxia and hyperoxia.Hyperoxia, alone or synergistically with temozolomide, activated the UPR in sensitive and resistant D54 and U87 cell lines. Hyperoxia also reduced survival benefit of U87 and U251 cells with P4HB overexpression through the UPR.Hyperoxia enhanced GBM cell sensitivity to temozolomide, likely through UPR, highlighting an important treatment modality targeting chemosensitive and -resistant GBM.

In this paper, 2 metal layers, very fine pitch Cu RDL process using spin-on photo-pattern-able polymer based material was demonstrated, with Cu wiring of a minimum of 2-μm/2-μm line/space (L/S) and dielectric via diameter of 2 μm. Electrical test structures were designed and fabricated to assess the performance of the Cu RDL process. Meander fork structures of 2-μm/2-μm L/S was used to measure the leakage current. The leakage current ranged from 1 to 6 pA for the different line lengths evaluated, indicating good insulation property of the polymer material. Daisy chain structure was used to measure the electrical resistance with different via numbers pitches. From the measurement, the resistance of the daisy chain structure increases with the number of vias. Single via resistance was also measured with Cross Bridge Kelvin Resistor (CBKR) structure. The measured contact resistance of 2-μm diameter via is ~20 mΩΣ The reliability of the Cu RDL process was also evaluated by subjecting the wafers to Unbiased Highly Accelerated Stress Test (uHAST). The daisy chain structures measurement shows no significant change in electrical resistance after the reliability test, indicating good reliability of the Cu RDL process.

Decaps are the panacea to cure the noise related issues. Due to the short distance advantage, decaps were embedded in the package instead of PCB. These decaps, generally having higher thickness than chips, would play a vital role in the wafer level molding process. Improper population will cause decap shift and incomplete fill issues. In the present paper, proper arrangement of decaps were designed and optimized. The results show that decaps placed along two adjacent sides rather than two opposite sides of the chip would result in better filling. In order to further reduce the drag force on decaps, chip to decap distance should be as large as possible. This implies that narrow gaps would result in higher drag force. Therefore, narrow gaps should be avoided to ease the drag force in the package as well as the whole wafer.

To the Editor: The Abciximab in Ischemic Stroke Investigators reported the encouraging results of their randomized, double-blind, placebo-controlled, dose-escalation trial.1 Of 74 eligible and consenting patients presenting within 24 hours of onset of their ischemic stroke, 54 patients were treated with 4 escalating doses of intravenous abciximab and 20 patients with placebo. The scheduled post-study CT brain scan detected asymptomatic parenchymal hemorrhages in 7% of abciximab-treated patients and 5% of placebo-treated patients; another 11% of abciximab-treated patients had asymptomatic parenchymal hemorrhages on unscheduled brain imaging (CT or MRI) performed on days 2 through 35. Symptomatic hemorrhagic transformation was not seen, while asymptomatic parenchymal hemorrhages were associated with a higher baseline National Institute of Health Stroke Scale (NIHSS) score. We would raise the following issue for clarification by the authors and report our limited experience of using abciximab in Chinese stroke patients. Concomitant use of antithrombotic medications during the time period of diagnosing parenchymal hemorrhage was listed in Table 3 of the article.1 The scheduled CT brain scan detected asymptomatic parenchymal hemorrhages in patients A, D, G, H, and I, who also received concomitant antithrombotic medications, such as systemic heparin, low-dose heparin, aspirin, and warfarin sodium. Nevertheless, the study protocol required that antiplatelet agents or anticoagulants not be administered until the results of the scheduled CT brain scan became available (as …

In the past, there has been a plausible hypothesis that anterior cruciate ligament graft placement at isometric sites, such that the tibial and femoral attachment sites remain equidistant from each other throughout knee range of motion, would increase the likelihood of a satisfactory outcome. For a given tibial placement we wanted to determine whether placing the graft on the average of the most isometric femoral line, a fixed distance from the outlet of the intercondylar notch, would return normal laxity to all knees. The three-dimensional kinematics of seven cadaveric knees were measured for angles from full extension to 90° of flexion at 15° increments. Physiologic levels of quadriceps muscle forces were applied to the intact knee, after transection of the anterior cruciate ligament, and after ligament reconstruction with a patellar tendon graft. On average, the reconstruction was found to return anterior-posterior translation, internal-external rotation, and varus-valgus rotation to levels not significantly different from those of the intact knee. However, the ranges of the translation and rotations were large. Placing the graft on the average most isometric femoral line did not restore knee laxity to normal in all knees. This supports the need to customize graft placement in each knee at the time of surgery.

To understand the clinical features, antimicrobial therapy, and epidemiology of Chryseobacterium indologenes infections, the medical records of 36 patients with nosocomial Chryseobacterium indologenes infections seen over a three-year period at National Taiwan University Hospital were reviewed. The 36 isolates recovered from these patients were studied by molecular typing and determination of antimicrobial susceptibility patterns. Nine patients had underlying neoplastic diseases, seven had diabetes mellitus, five had burn wounds, and four had uremia. The clinical syndrome included ten patients with intraabdominal infections, nine with wound sepsis, six with intravascular catheter-related bacteremia, and four with ventilator-associated pneumonia. Thirteen patients had monomicrobial bacteremia, and four had polymicrobial bacteremia. Nineteen patients (53%) developed infections associated with various indwelling devices. The deaths of five patients (14%) were directly attributable to infection with Chryseobacterium indologenes. All isolates recovered showed a wide range of resistance to commonly used antimicrobial agents. The random amplified polymorphic DNA (RAPD) patterns of the isolates differed from each other, indicating the absence of epidemiological relatedness among these isolates. Nosocomial infection caused by multiresistant Chryseobacterium indologenes appears to be an emerging problem in Taiwan and should be studied further.

CHROMagar Liquid ECC (CLECC) was compared with membrane lauryl sulphate broth plus urea (mLS-UA) used routinely in Hong Kong for E. coli enumeration. E. coli appear as distinctive greenish-blue colonies on CLECC while other faecal coliforms are red in colour. CLECC performance was comparable to mLS with mixtures of faecal coliforms, E. coli and non-faecal coliforms. Beach, river, ground and waste water samples were used for further comparison. Results given by the two media were significantly correlated (P =

Various highly regulated, complex signaling pathways govern the lineage-specific differentiation of mesenchymal stem cells (MSCs). The unique properties of MSCs have allowed us to characterize the differentiation pathways and proliferative stimuli of these lineages. While the specific signaling cascades controlling differentiation and proliferation are unique among each lineage, some pathways are critical in the differentiation of multiple lineages. Furthermore, a considerable amount of crosstalk exists between the major signaling pathways. The TGF-β superfamily has significant effects on proliferation and differentiation, including key roles in osteogenic and chondrogenic differentiation. Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily with well-described effects on osteogenesis and chondrogenesis. Demonstrating crosstalk with BMPs, other signaling pathways implicated in osteogenic and chondrogenic differentiation include the Wnt signaling pathway and the FGF family. Hedgehog and notch signaling also crosstalk with Wnts, with diverse effects on osteogenic, myogenic and adipogenic differentiation. PPARγ is the master regulator of adipogenesis and is essential for the induction of normal adipogenesis, and C/EBPs modulate the expression and function of PPARγ. Crosstalk exists between the major signaling pathways governing adipogenesis and osteogenesis, as differential expression of BMPs and PPARγ significantly alters adipogenic and osteogenic differentiation. While the major signaling pathways mediating lineage-specific differentiation are well-studied, the complex crosstalk between these pathways and lineage-specific cascades makes elucidation of specific mechanisms quite difficult.

The effects of an ice wrap, applied to a knee for 20 minutes, on blood flow and bone metabolism were measured using triple-phase technetium bone scans. Twenty-one subjects between 29 and 63 years of age were studied. A commercially available ice wrap was applied to one knee 20 minutes before scanning, while an identical wrap left at room temperature was applied to the opposite knee to act as a control. Scans of the knees were obtained at the completion of cooling, and the images were quantified by computer image analysis for each knee at each phase of the scan. Percentage of decrease in blood flow and subsequent bone uptake of technetium for the iced knee as compared with the op posite knee were calculated. All iced knees demon strated decreased arterial and soft tissue blood flow as well as decreased bone uptake, which is a reflection of changes in both bone blood flow and metabolism. The average decrease was 38.4% ± 4.97 in arterial blood flow, 25.8% ± 2.04 in soft tissue blood flow, and 19.3% ± 2.0 (standard error of the mean in each) in bone up take. This "ice effect" was not related to age, sex, knee circumference, or skin temperature after cooling. By de creasing blood flow and cell metabolism, ice theoreti cally can limit hemorrhage and cell death in the setting of acute traumatic injury. This study thus provides a scientific rationale for the use of ice as tested for such injuries to a large joint, whether in the soft tissues or bones.

The balloon-expandable, stainless steel, flexible coil stent is a useful device for managing acute or threatened closure after percutaneous transluminal coronary angioplasty.1–5 Use of the device is associated with thrombosis of the stented vessel in a small but important group of patients.3,6–10 The clinical, angiographic, and procedural factors associated with stent thrombosis with this device are still unknown. The objective of this study was to define predictors of stent thrombosis occurring within the ftrst month after stenting with this device.

A full color display with its spectra covering the entire visible color range using a single polymer is presented here. Different concentrations of poly(2,6-[4-phenylquinoline]) and poly(2,6-[p-phenylene]-4-phenylquinoline) were incorporated into silica gels via the sol–gel technique. At high concentrations, the conjugated polymers form multiple excimers in the channels within the silica network, leading to the emission of red light (∼600 nm). At low concentrations, the polymer chains are isolated and are being trapped individually in the silica domain, which results in the emission of blue light (∼400 nm). For concentrations in-between, moderate extensive chain interaction leads to the emission of green, yellow, and orange colors. Therefore, the color tunability can be achieved by simply varying the concentration of quinoline polymers in the silica glasses.

We introduce the quantum theory of the electron spin decoherence in a nuclear spin bath and the dynamical decoupling approach for protecting the electron spin coherence. These theories are applied to various solid‐state systems, such as radical spins in molecular crystals and NV centers in diamond.

Low temperature bonds are thin intermetallic bonds that are formed between devices when plated layers of different metals on each side of the component come into contact under relatively low temperature and high pressure. These joints comprised completely of intermetallic compounds, will fail in a sudden unexpected manner, compared to normal solder joints which fail in a ductile manner where cracks grow more slowly. This problem of weak interconnects is further exacerbated when these thin interconnections are formed on pads located above through-silicon vias (TSVs). When a change in temperature occurs, the mismatch in coefficient of thermal expansion (CTE) causes the copper inside the TSV to expand or contract much more than the surrounding silicon. This could result in unexpectedly high tensile stresses in the joints. This additional tensile stress on post-formation cooling to room temperature increases the likelihood of joint failure. This paper presents a novel pad design to overcome the situation of high stress in the joints. The proposed design does not involve any additional fabrication or material cost. Simulation results show that with the proposed pad design, the maximum tensile stress in the interconnect decreases by 50%. Reliability assessment has also done in order to compare the proposed pad design with the conventional design. It is found that the samples with the proposed design have a better drop impact reliability performance and higher shear strength than the samples with the usual pad design.

No single etiology regarding the cause of osteochondritis dissecans (OCD) lesions is unanimously accepted. This report documents a novel case of multiple OCD lesions affecting the left knee and a solitary defect of the right elbow in a patient with acquired human growth hormone (hGH) deficiency and supplementation. hGH deficiency and hormone replacement may be related to the development of OCD lesions.

AIMS: To evaluate the use of a cppB gene derived polymerase chain reaction (PCR) assay for direct detection of Neisseria gonorrhoeae in clinical samples. METHODS: A PCR assay was performed on 33 N gonorrhoeae strains and 12 other Neisseria species and other normal genital flora to evaluate the specificity of the chosen cppB primers. The assay was subsequently evaluated with 52 clinical swab samples collected from China. RESULTS: An amplified product of 390 base pairs (bp) was observed with all the N gonorrhoeae strains, each of these products on digestion with the restriction enzyme MspI produced two bands of 250 bp and 140 bp respectively. This set of primers did not produce any amplified product of the expected length with the other non-gonococcal strains tested. For the 52 clinical swabs, 34 were culture positive and PCR successfully detected all these positives. In addition the PCR was positive for two swabs which were culture negative but positive for N gonorrhoeae antigens when tested with the ELISA method (Gonozyme). CONCLUSIONS: This PCR assay is a promising diagnostic tool for detection of gonococci directly from clinical swab samples. Further evaluation is necessary.

This paper focused on design, assembly and reliability assessments of 21 × 21 mm2 Cu/Low-K Flip Chip (65 nm technology) with 150 ?m bump pitch. Metal redistribution layer (RDL) and polymer encapsulated dicing lane (PEDL) were applied to the chip wafer to reduce the shear stress on the Cu/low-K layers and also the strain on the solder bumps. The first level interconnects evaluated were Pb-free (97.5Sn2.5Ag), High-Pb (95Pb5Sn) and Cu-post/95Pb5Sn. Two different die thicknesses, such as 750 ?m and 300 ?m, were evaluated. the flip chip assembly of high-pb test vehicles required the right choice of flux and special alignment between the high-pb solder bumps and substrate presolder to ensure proper solder bumps and substrate pre-solder alloy wetting. Finite Element Modeling (FEM) was performed to investigate the impact of different underfill, on the inelastic strain of the outermost bumps and shear stress in the Cu/low-K layer. JEDEC standard reliability were performed on the test vehicles with different first level interconnects, die thickness, underfill materials and dicing methods.

The annual incidence of typhoid fever in Taiwan was 2.1-3.6 cases per 1,000,000 population from 1995 to 2002. More than 80% of 45 patients with typhoid fever treated at National Taiwan University Hospital from 1996 to 2002 had elevated serum aminotransferase levels at presentation. Ten of these patients were treated during an outbreak in Taipei County in 2002, and seven of them who did not have pre-existing liver disease developed hepatitis, which was unrelated to other aetiologies. All Salmonella typhi isolates were susceptible to extended-spectrum cephalosporins and fluoroquinolones. Multidrug resistance (intermediate resistance to ampicillin, trimethoprim-sulphamethoxazole, and chloramphenicol) was found in one (2.5%) of the 40 isolates studied. Pulsed-field gel electrophoresis analysis demonstrated a high genetic diversity among S. typhi isolates and identified a novel clone associated with the 2002 outbreak. Physicians should be alert to the possibility of typhoid fever when patients, without other gastrointestinal symptoms, present with sustained fever and hepatitis.

The annual incidence of meningococcal disease (meningitis and septicaemia) in Taiwan was 0·94/105 population in 1953. It then declined to below 0·001 from 1980 to 1987, and re-emerged in 2000 with a rate of 0·07/105 population. In 2001 there was a further increase in incidence (43 cases, 0·19/105). Of 43 isolates of Neisseria meningitidis available for this study, including 41 from patients treated in 2001, three (7·0%) were penicillin insensitive (MIC [ges ]0·12 μg/ml), though all were β-lactamase negative; 16 (37·2%) were resistant to trimethoprim–sulphamethoxazole sulphamethoxazole (MIC [ges ]4/76 μg/ml). Serogrouping and genotype analysis revealed nine domestic clones. None of the 43 patients had any relationship (travel or contact history) with the 2000 or 2001 Hajj pilgrimage. Epidemiological information and typing results suggested wide dissemination of a limited number of domestic clones of N. meningitidis, manifesting as serogroups W-135, B and Y. Two clones of serogroup W-135 involved in the outbreak were genetically distinct from the 2000 or 2001 Hajj-related W-135 clone.

In a previous study we used technetium-99m bone scans to show that cooling a knee for 20 minutes with a standard ice wrap will decrease soft tissue blood flow by a mean of 26%, and skeletal blood flow and me tabolism by 19%. The present study examined the ef fects of shorter and longer icing periods to determine minimum cooling time for a measurable and consistent decrease, and time to produce maximal decrease within a safe period of icing (

Ischaemic nephropathy is currently a major public health issue in atherosclerotic populations. Although atherosclerotic cardiovascular disease in Asia has reached epidemic proportions over the last two decades, there is little published data on the prevalence of atherosclerotic renal artery stenosis (ARAS) in Oriental subjects. Because ARAS may be clinically silent until end-stage renal failure sets in, it is important to identify patients with significant but clinically unsuspected ARAS. ARAS and coronary artery disease (CAD) often coexist.The purpose of the present study was to evaluate the prevalence and predictors of ARAS among Chinese patients with CAD.A total of 230 consecutive Chinese patients with CAD confirmed by coronary angiography underwent an abdominal aortogram in the same sitting to screen for ARAS. Patient demographics and comorbidities were analysed for any association with ARAS.A total of 34 (14.8%) patients was found to have significant ARAS. Age and multivessel CAD were independent predictors of ARAS. Hypertension, renal insufficiency, extracranial cerebrovascular disease and female gender were also associated with a higher risk of ARAS but did not independently predict ARAS.Clinically silent yet angiographically significant ARAS is common among CAD patients. The prevalence and predictors of ARAS among Chinese patients with CAD are similar to those reported for Caucasian subjects. Underlying ARAS should be suspected in CAD patients with such comorbidities as hypertension, renal insufficiency, extracranial cerebrovascular disease, and more so in the elderly and those with multivessel disease.

The activated product of the myc oncogene deregulates both cell growth and death check points and, in a permissive environment, rapidly accelerates the affected clone through the carcinogenic process. Advances in understanding the molecular mechanism of Myc action are highlighted in this review. With the revolutionary developments in molecular diagnostic technology, we have witnessed an unprecedented advance in detecting activated myc in its deregulated, oncogenic form in primary human cancers. These improvements provide new opportunities to appreciate the tumor subtypes harboring deregulated Myc expression, to identify the essential cooperating lesions, and to realize the therapeutic potential of targeting Myc. Knowledge of both the breadth and depth of the numerous biological activities controlled by Myc has also been an area of progress. Myc is a multifunctional protein that can regulate cell cycle, cell growth, differentiation, apoptosis, transformation, genomic instability, and angiogenesis. New insights into Myc's role in regulating these diverse activities are discussed. In addition, breakthroughs in understanding Myc as a regulator of gene transcription have revealed multiple mechanisms of Myc activation and repression of target genes. Moreover, the number of reported Myc regulated genes has expanded in the past few years, inspiring a need to focus on classifying and segregating bona fide targets. Finally, the identity of Myc-binding proteins has been difficult, yet has exploded in the past few years with a plethora of novel interactors. Their characterization and potential impact on Myc function are discussed. The rapidity and magnitude of recent progress in the Myc field strongly suggests that this marvelously complex molecule will soon be unmasked.

During the period from August 1994 to October 1998, a total of 19 isolates of Exophiala jeanselmei were recovered from 17 patients with various underlying thoracic diseases treated at National Taiwan University Hospital. The purpose of this study was to describe the clinical characteristics of these patients and to determine the microbiologic relatedness of the E. jeanselmei.Of the 19 isolates, 11 from nine patients were preserved and were identified based on their biotypes as determined by the API ID32C System, their cellular fatty acid profiles by gas-liquid chromatography, their antibiotypes to five antifungal agents by the E-test, and their random amplified polymorphic DNA (RAPD) patterns by arbitrarily primed PCR. Extensive environmental surveillance cultures and cultures from the skin of eight patients and hands of one physician were also performed.One of the 17 patients had E. jeanselmei isolated from cutaneous phaeohyphomycosis (3 isolates), and the other 16 patients had isolations from pleural effusion specimens (15 isolates) or lung mass (1 isolate) following sonography-guided aspiration. The latter 16 patients had no clinical or pathologic evidence of fungal infection. Isolates (clone 1) from aspirated specimens had identical biotypes, antibiotypes, and RAPD patterns, which were different from those of the three isolates (clone 2) from the patient with a cutaneous lesion. All specimens from environmental sources, patients' skin, and the hands of the physician were negative for E. jeanselmei.This series of patients demonstrates the difficulty in identifying the sources of a nosocomial pseudoinfection due to this slow-growing microorganism when isolated from pleural effusion specimens.

In order to understand virulence factors of Chryseobacterium indologenes isolates associated with invasive infection, enzymatic activities and cellular fatty acid profiles of 42 isolates recovered at National Taiwan University Hospital from January 1994 to December 1996 were studied. Among them, 12 blood isolates were considered as invasive and 30 (recovered from urine, sputa, infected burn wounds, and catheter tips) were noninvasive. All isolates showed strong activities of alkaline phosphatase, acid phosphatase, naphthol-AS-BI-phosphohydrolase, and N-acetyl-beta-glucosaminidase, and had no activities for alpha-galactosidase, beta-galactosidase, beta-glucuronidase, alpha-mannosidase, and alpha-fucosidase. The activities of other enzymes were variable. Thirty-two isolates (76%) had varying degrees of protease activity. Two profiles (profiles I and II) of cellular fatty acids of the isolates were found and profile I predominated. There was no significant difference of distribution of cellular fatty acid profiles and activities of enzymes between invasive and noninvasive isolates, except protease activity which was significantly higher in invasive isolates than that in noninvasive isolates. Protease activity may play an important role in virulence on invasive infections caused by C. indologenes.