Unraveling diffusion behavior in Cu-to-Cu direct bonding with metal passivation layers.

Cu/SiO2 hybrid bonding presents a promising avenue for achieving high-density interconnects by obviating the need for microbumps and underfills. Traditional copper bonding methods often demand temperatures exceeding 400 °C, prompting recent endeavors to mitigate bonding temperatures through investigations into metal passivation bonding. In this study, we scrutinized the diffusion behavior associated with various metal passivation layers (Platinum, Titanium, Tantalum, and Chromium) in the context of low-temperature direct copper bonding and delved into the essential bonding mechanisms. We observed a deviation from conventional metal-metal bonding factors, such as surface roughness and grain size, in the diffusion behavior. Remarkably, our analysis revealed a pronounced correlation between the crystallinity of the metal passivation layers and diffusion behavior, surpassing the influence of other experimental factors. Subsequent post-bonding examinations corroborated consistent diffusion behavior in Pt and Cr passivation samples with disparate crystallinities, reinforcing the significance of crystallinity in the bonding process. Our findings underscore crystallinity as a pivotal factor governing diffusion behavior, even under varied bonding conditions. These insights are instrumental in achieving exceptional bonding characteristics at lower temperatures in Cu/SiO2 hybrid bonding. Implications of this study extend to the prospect of advancing highly integrated systems through die-to-wafer bonding, marking a substantial stride toward future applications.

Validation of comprehensive complication index in the general surgery department of a small-volume hospital: A prospective observational study.

BACKGROUND/OBJECTIVE: The comprehensive complication index (CCI) was developed following the Clavien-Dindo classification (CDC) to more properly reflect various complications that occur in one patient. In this study, we performed a prospective observational study to validate the usefulness of CCI in a small-volume hospital. METHODS: From March 2017 to February 2018, among the patients who had scheduled surgery with general anesthesia in the Department of Surgery in St. Paul hospital in Korea, 240 patients were enrolled after informed consent. A minor-risk surgery, such as appendectomy, and surgery for inguinal hernia were excluded. The complications were estimated in both CDC and CCI in each patient. Patients were investigated with the EORCT-C30 quality of life questionnaire before and after surgery, and the relationship between CCI score and change in the quality of life was evaluated. RESULTS: There were 26 (10.83%), 41 (17.08%), 8 (3.33%), 3 (1.25%), 4 (1.67%), and 2 (0.83%) patients who were classified as grades I, II, IIIa, IIIb, IVa, and IVb, respectively. The average CCI was 22.94 ± 12.79, and distribution ranged from 8.66 to 76.40. CCI was well distributed in patients with complications more than CDC grade. While there was no correlation between preoperative Charlson comorbidity index with CCI, pain scale, and cognitive scale were aggravated significantly when CCI increased. CONCLUSION: CCI reflected the complication status with a more detailed distribution compared with CDC. Moreover, CCI had a significant relation with pain and the cognitive function scale. CCI might be a useful complication grading system in a small-volume surgical department.

Prevalence of Malnutrition in Hospitalized Patients: a Multicenter Cross-sectional Study.

BACKGROUND: Malnutrition is associated with many adverse clinical outcomes. The present study aimed to identify the prevalence of malnutrition in hospitalized patients in Korea, evaluate the association between malnutrition and clinical outcomes, and ascertain the risk factors of malnutrition. METHODS: A multicenter cross-sectional study was performed with 300 patients recruited from among the patients admitted in 25 hospitals on January 6, 2014. Nutritional status was assessed by using the Subjective Global Assessment (SGA). Demographic characteristics and underlying diseases were compared according to nutritional status. Logistic regression analysis was performed to identify the risk factors of malnutrition. Clinical outcomes such as rate of admission in intensive care units, length of hospital stay, and survival rate were evaluated. RESULTS: The prevalence of malnutrition in the hospitalized patients was 22.0%. Old age (≥ 70 years), admission for medical treatment or diagnostic work-up, and underlying pulmonary or oncological disease were associated with malnutrition. Old age and admission for medical treatment or diagnostic work-up were identified to be risk factors of malnutrition in the multivariate analysis. Patients with malnutrition had longer hospital stay (SGA A = 7.63 ± 6.03 days, B = 9.02 ± 9.96 days, and C = 12.18 ± 7.24 days, P = 0.018) and lower 90-day survival rate (SGA A = 97.9%, B = 90.7%, and C = 58.3%, P < 0.001). CONCLUSION: Malnutrition was common in hospitalized patients, and resulted in longer hospitalization and associated lower survival rate. The rate of malnutrition tended to be higher when the patient was older than 70 years old or hospitalized for medical treatment or diagnostic work-up compared to elective surgery.

Dependence of Grain Size on the Performance of a Polysilicon Channel TFT for 3D NAND Flash Memory.

We investigated the dependence of grain size on the performance of a polycrystalline silicon (poly-Si) channel TFT for application to 3D NAND Flash memory devices. It has been found that the device performance and memory characteristics are strongly affected by the grain size of the poly-Si channel. Higher on-state current, faster program speed, and poor endurance/reliability properties are observed when the poly-Si grain size is large. These are mainly attributed to the different local electric field induced by an oxide valley at the interface between the poly-Si channel and the gate oxide. In addition, the trap density at the gate oxide interface was successfully measured using a charge pumping method by the separation between the gate oxide interface traps and traps at the grain boundaries in the poly-Si channel. The poly-Si channel with larger grain size has lower interface trap density.

Comparison of Long-Term Outcomes Between Emergency Surgery and Bridge to Surgery for Malignant Obstruction in Right-Sided Colon Cancer: A Multicenter Retrospective Study.

BACKGROUND: Malignant obstruction in right-sided colon (MORC) has traditionally been treated by emergency resection with primary anastomosis. The aim of this study was to evaluate short-term postoperative and long-term oncologic outcomes according to the surgical approach adopted for MORC. METHODS: A total of 1785 patients who underwent curative surgery for stage II or III colon cancer in seven hospitals were reviewed retrospectively. Seventy-four of 1785 patients had MORC. We compared the postoperative outcome and long-term oncologic outcome between the emergency surgery (ES) group (49 patients) and the bridge to surgery (BS) group (25 patients) for 74 patients with MORC. RESULTS: There were no differences in the length of the distal and proximal resection margin (p = 0.820 and p = 0.620) or the number of metastatic lymph nodes (p = 0.221). There were no differences in flatus passage (p = 0.242), start of diet (p = 0.336), hospital stay (p = 0.444), or postoperative morbidity (p = 0.762). The 5-year overall survival rates were 73.2 % in the ES group and 90.7 % in the BS group (p = 0.172). Moreover, the 5-year disease-free survival rates were 71.9 % in the ES group and 76.2 % in the BS group (p = 0.929). CONCLUSIONS: On the basis of the above results, the postoperative course of the ES group was similar to that of the BS group. In addition, the long-term oncologic outcome of the BS group was similar or slightly better than that of the ES group. BS after colonic stent may be an alternative option for MORC.

Recurrent cervical esophageal stenosis after colon conduit failure: use of myocutaneous flap.

A 53-year-old male developed cervical esophageal stenosis after esophageal bypass surgery using a right colon conduit. The esophageal bypass surgery was performed to treat multiple esophageal strictures resulting from corrosive ingestion three years prior to presentation. Although the patient underwent several endoscopic stricture dilatations after surgery, he continued to suffer from recurrent esophageal stenosis. We planned cervical patch esophagoplasty with a pedicled skin flap of sternocleidomastoid (SCM) muscle. Postoperative recovery was successful, and the patient could eat a solid meal without difficulty and has been well for 18 mo. SCM flap esophagoplasty is an easier and safer method of managing complicated and recurrent cervical esophageal strictures than other operations.

Determination of work function of graphene under a metal electrode and its role in contact resistance.

Although the work function of graphene under a given metal electrode is critical information for the realization of high-performance graphene-based electronic devices, relatively little relevant research has been carried out to date. In this work, the work function values of graphene under various metals are accurately measured for the first time through a detailed analysis of the capacitance-voltage (C-V) characteristics of a metal-graphene-oxide-semiconductor (MGOS) capacitor structure. In contrast to the high work function of exposed graphene of 4.89-5.16 eV, the work function of graphene under a metal electrode varies depending on the metal species. With a Cr/Au or Ni contact, the work function of graphene is pinned to that of the contacted metal, whereas with a Pd or Au contact the work function assumes a value of ∼4.62 eV regardless of the work function of the contact metal. A study of the gate voltage dependence on the contact resistance shows that the latter case provides lower contact resistance.

Graphene gate electrode for MOS structure-based electronic devices.

We demonstrate that the use of a monolayer graphene as a gate electrode on top of a high-κ gate dielectric eliminates mechanical-stress-induced-gate dielectric degradation, resulting in a quantum leap of gate dielectric reliability. The high work function of hole-doped graphene also helps reduce the quantum mechanical tunneling current from the gate electrode. This concept is applied to nonvolatile Flash memory devices, whose performance is critically affected by the quality of the gate dielectric. Charge-trap flash (CTF) memory with a graphene gate electrode shows superior data retention and program/erase performance that current CTF devices cannot achieve. The findings of this study can lead to new applications of graphene, not only for Flash memory devices but also for other high-performance and mass-producible electronic devices based on MOS structure which is the mainstream of the electronic device industry.

Clinical Significance of Lymph Node Ratio in Stage III Colorectal Cancer.

PURPOSE: Recent literature has shown that lymph node ratio is superior to the absolute number of metastatic lymph nodes in predicting the prognosis in several malignances other than colorectal cancer. The aim of this study was to evaluate the prognostic significance of the lymph node ratio (LNR) in patients with stage III colorectal cancer. METHODS: We included 186 stage III colorectal cancer patients who underwent a curative resection over a 10-year period in one hospital. The cutoff point of LNR was chosen as 0.07 because there was significant survival difference at that LNR. The Kaplan-Meier and the Cox proportional hazard models were used to evaluate the prognostic effect according to LNR. RESULTS: There was statistically significant longer overall survival in the group of LNR > 0.07 than in the group of LNR ≤ 7 (P = 0.008). Especially, there was a survival difference for the N1 patients group (LN < 4) according to LNR (5-year survival of N1 patients was lower in the group of LNR > 0.07, P = 0.025), but there was no survival difference for the N2 group (4 ≥ LN) according to LNR. The multivariate analysis showed that the LNR is an independent prognostic factor. CONCLUSIONS: LNR can be considered as a more accurate and potent modality for prognostic stratifications in patients with stage III colorectal cancer.

Lysyl oxidase G473A polymorphism is closely associated with susceptibility to gastric cancer in a South Korean population.

The aim of this study was to determine whether a single nucleotide polymorphism at G473A (rs1800449) within the LOX-propeptide is associated with susceptibility to gastric cancer. We investigated the genotype and allele frequencies of this gene in tissue specimens from 458 gastric cancer patients and 282 healthy individuals. Polymorphism analysis was performed by amplifying the propeptide region of LOX and digestion with NotI followed by sequencing of the products. The frequencies of the LOX G473A G/G, G/A, and A/A genotypes were 54.4% (249/458), 34.3% (157/458), and 11.3% (52/458), respectively, in gastric cancer patients and 58.9% (166/300), 35.5% (100/282), and 5.7% (16/282), respectively, in the healthy controls. Statistically significant differences in the genotype and allele frequency of LOX rs1800449 were observed between the healthy controls and gastric cancer patients (p = 0.0294 and p = 0.0339). When the data were stratified according to gastric cancer histologic subtype, the risk of diffuse-type gastric cancer in carriers with an A allele (G/A or A/A genotypes) was statistically higher compared to that of carriers with the G/G genotype (p = 0.0001). Our findings suggest that G473A polymorphism of the LOX gene may be closely associated with susceptibility to the development and differentiation of gastric cancer in South Korean patients.

Is conservative treatment with antibiotics the correct strategy for management of right colonic diverticulitis?: a prospective study.

PURPOSE: The goals of this study were to identify whether conservative treatment with antibiotics in right colonic diverticulitis (RCD) patients, our empirical method used until now, is adequate and to determine how the natural history of RCD is affected by conservative treatment. METHODS: This study was designed as a case-control study. Group I was comprised of 12 patients who were managed conservatively, and clinical data were retrospectively collected. In group II, a total of 49 patients, diagnosed by using diagnostic criteria for RCD and managed conservatively, were prospectively included. RESULTS: The period of fasting was 2.7 days, and the hospital stay was 4.6 days in all patients. The intravenous and the oral antibiotic periods were 3.8 days and 9.8 days, respectively. There were no statistically significant differences in treatment results between the two groups except the duration of fasting and the hospitalization, and there were no complications under conservative treatment. Eight patients (13.1%) had recurrent diverticulitis during the follow-up period. The recurrence risk showed no significant difference between the groups. The RCD-free period after management was 60.1 months, and patients with recurrent RCD were treated by conservative treatment or laparoscopic surgery. CONCLUSION: Conservative treatment with antibiotics is the optimal treatment of choice for RCD and shows no increase in complications.

Prognostic value of CEA and CA 19-9 tumor markers combined with cytology from peritoneal fluid in colorectal cancer.

BACKGROUND: Early diagnosis and management of peritoneal metastases from colorectal cancer patients are difficult clinical challenges. The aims of this study were to evaluate the clinical significance of tumor markers and cytology in peritoneal effusions (PE) and peritoneal irrigation fluid (PI) and to determine their value as prognostic indicators in this disease. METHODS: Two hundred thirty-four consecutive patients who underwent abdominal surgery for colorectal cancer from January 2006 to December 2007 were included, and tumor markers and cytology in PE and PI were analyzed prospectively. RESULTS: The incidence of free cancer cells retrieved from peritoneal samples was 7.9%. Cytology was positive in 40.0% by Papanicolaou and Giemsa staining, 73.3% by hematoxylin and eosin staining of cell blocks, and 66.7% by carcinoembryonic antigen (CEA) and calretinin immunohistochemistry. Multivariate analysis revealed that peritoneal CEA and cancer antigen (CA) 19-9 in PI were correlated with peritoneal metastasis and cytology. Level of peritoneal fluid CEA was statistically significantly correlated with recurrence and peritoneal metastatic recurrence in patients with negative peritoneal cytology. Cytology, peritoneal CEA, and peritoneal CA 19-9 showed correlations with cancer-free survival and overall survival. CONCLUSIONS: These correlations demonstrate the importance of continuous follow-up of peritoneal metastasis if there is positive cytology or an increase in CEA and CA 19-9 in peritoneal fluid.

A comprehensive analysis of the dual roles of BMPs in regulating adipogenic and osteogenic differentiation of mesenchymal progenitor cells.

Pluripotent mesenchymal stem cells (MSCs) are bone marrow stromal progenitor cells that can differentiate into osteogenic, chondrogenic, adipogenic, and myogenic lineages. Several signaling pathways have been shown to regulate the lineage commitment and terminal differentiation of MSCs. Here, we conducted a comprehensive analysis of the 14 types of bone morphogenetic protein (BMPs) for their abilities to regulate multilineage specific differentiation of MSCs. We found that most BMPs exhibited distinct abilities to regulate the expression of Runx2, Sox9, MyoD, and PPARgamma2. Further analysis indicated that BMP-2, BMP-4, BMP-6, BMP-7, and BMP-9 effectively induced both adipogenic and osteogenic differentiation in vitro and in vivo. BMP-induced commitment to osteogenic or adipogenic lineage was shown to be mutually exclusive. Overexpression of Runx2 enhanced BMP-induced osteogenic differentiation, whereas knockdown of Runx2 expression diminished BMP-induced bone formation with a decrease in adipocyte accumulation in vivo. Interestingly, overexpression of PPARgamma2 not only promoted adipogenic differentiation, but also enhanced osteogenic differentiation upon BMP-2, BMP-6, and BMP-9 stimulation. Conversely, MSCs with PPARgamma2 knockdown or mouse embryonic fibroblasts derived from PPARgamma2(-/-) mice exhibited a marked decrease in adipogenic differentiation, coupled with reduced osteogenic differentiation and diminished mineralization upon BMP-9 stimulation, suggesting that PPARgamma2 may play a role in BMP-induced osteogenic and adipogenic differentiation. Thus, it is important to understand the molecular mechanism behind BMP-regulated lineage divergence during MSC differentiation, as this knowledge could help us to understand the pathogenesis of skeletal diseases and may lead to the development of strategies for regenerative medicine.

CCN1/Cyr61 is regulated by the canonical Wnt signal and plays an important role in Wnt3A-induced osteoblast differentiation of mesenchymal stem cells.

Marrow mesenchymal stem cells are pluripotent progenitors that can differentiate into bone, cartilage, muscle, and fat cells. Wnt signaling has been implicated in regulating osteogenic differentiation of mesenchymal stem cells. Here, we analyzed the gene expression profile of mesenchymal stem cells that were stimulated with Wnt3A. Among the 220 genes whose expression was significantly changed by 2.5-fold, we found that three members of the CCN family, CCN1/Cyr61, CCN2/connective tissue growth factor (CTGF), and CCN5/WISP2, were among the most significantly up-regulated genes. We further investigated the role of CCN1/Cyr61 in Wnt3A-regulated osteogenic differentiation. We confirmed that CCN1/Cyr61 was up-regulated at the early stage of Wnt3A stimulation. Chromatin immunoprecipitation analysis indicates that CCN1/Cyr61 is a direct target of canonical Wnt/beta-catenin signaling. RNA interference-mediated knockdown of CCN1/Cyr61 expression diminished Wnt3A-induced osteogenic differentiation. Furthermore, exogenously expressed CCN1/Cyr61 was shown to effectively promote mesenchymal stem cell migration. These findings suggest that tightly regulated CCN1/Cyr61 expression may play an important role in Wnt3A-induced osteoblast differentiation of mesenchymal stem cells.

An orthotopic model of human osteosarcoma growth and spontaneous pulmonary metastasis.

Osteosarcoma is the most common primary malignancy of bone and patients often develop pulmonary metastases. In order to investigate the pathogenesis of human osteosarcoma, there is a great need to develop a clinically relevant animal model. Here we report the development of an osteosarcoma animal model using three related human osteosarcoma lines, the parental TE-85 and two derivative lines MNNG/HOS and 143B. In vitro characterization demonstrated that the 143B line had the greatest cell migration and the least cell adhesion activities among the three lines. The 143B line also exhibited the greatest ability for anchorage independent growth. When GFP-tagged osteosarcoma cells were injected into the proximal tibia of athymic mice, we found that 143B cells were highly tumorigenic and metastatic, and MNNG/HOS cells were tumorigenic but significantly less metastatic. TE85 cells were neither tumorigenic nor metastatic. The number of pulmonary metastases was found 50-fold higher in 143B injected animals than that in MNNG/HOS injected mice. No pulmonary metastases were detected in TE85 injected animals for up to 8 weeks. Primary tumors formed by MNNG/HOS and 143B cells could be visualized by whole body fluorescence imaging, while the pulmonary metastases were visualized on the necropsied samples. The GFP tagged 143B cells (and to a lesser extent, MNNG/HOS cells) were readily recovered from lung metastases. This clinically relevant model of human osteosarcoma provides varying degrees of tumor growth at the primary site and metastatic potential. Thus, this orthotopic model should be a valuable tool to investigate factors that promote or inhibit osteosarcoma growth and/or metastasis.

Wnt/beta-catenin signaling pathway as a novel cancer drug target.

Wnt proteins are a large family of secreted glycoproteins. Wnt proteins bind to the Frizzled receptors and LRP5/6 co-receptors, and through stabilizing the critical mediator beta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. Deregulation of the canonical Wnt/beta-catenin signaling pathway, mostly by inactivating mutations of the APC tumor suppressor, or oncogenic mutations of beta-catenin, has been implicated in colorectal tumorigenesis. Although oncogenic mutations of beta-catenin have only been discovered in a small fraction of non-colon cancers, elevated levels of beta-catenin protein, a hallmark of activated canonical Wnt pathway, have been observed in most common forms of human malignancies, indicating that activation of this pathway may play an important role in tumor development. Over the past 15 years, our understanding of this signaling pathway has significantly improved with the identification of key regulatory proteins and the important downstream targets of beta-catenin/Tcf transactivation complex. Given the fact that Wnt/beta-catenin signaling is tightly regulated at multiple cellular levels, the pathway itself offers ample targeting nodal points for cancer drug development. In this review, we discuss some of the strategies that are being used or can be explored to target key components of the Wnt/beta-catenin signaling pathway in rational cancer drug discovery.

Connective tissue growth factor (CTGF) is regulated by Wnt and bone morphogenetic proteins signaling in osteoblast differentiation of mesenchymal stem cells.

Osteoblast lineage-specific differentiation of mesenchymal stem cells is a well regulated but poorly understood process. Both bone morphogenetic proteins (BMPs) and Wnt signaling are implicated in regulating osteoblast differentiation and bone formation. Here we analyzed the expression profiles of mesenchymal stem cells stimulated with Wnt3A and osteogenic BMPs, and we identified connective tissue growth factor (CTGF) as a potential target of Wnt and BMP signaling. We confirmed the microarray results, and we demonstrated that CTGF was up-regulated at the early stage of BMP-9 and Wnt3A stimulations and that Wnt3A-regulated CTGF expression was beta-catenin-dependent. RNA interference-mediated knockdown of CTGF expression significantly diminished BMP-9-induced, but not Wnt3A-induced, osteogenic differentiation, suggesting that Wnt3A may also regulate osteoblast differentiation in a CTGF-independent fashion. However, constitutive expression of CTGF was shown to inhibit both BMP-9- and Wnt3A-induced osteogenic differentiation. Exogenous expression of CTGF was shown to promote cell migration and recruitment of mesenchymal stem cells. Our findings demonstrate that CTGF is up-regulated by Wnt3A and BMP-9 at the early stage of osteogenic differentiation, which may regulate the proliferation and recruitment of osteoprogenitor cells; however, CTGF is down-regulated as the differentiation potential of committed pre-osteoblasts increases, strongly suggesting that tight regulation of CTGF expression may be essential for normal osteoblast differentiation of mesenchymal stem cells.

Malignant gastrointestinal stromal tumor of the gallbladder.

Gastrointestinal stromal tumors (GISTs) of the gallbladder are representative of an extremely rare group of tumors. We have encountered a patient with a malignant GIST of the gallbladder and presented it with a review of some articles. A 72-yr-old woman initially presented with right upper quadrant abdominal pain, fever and chills. Emergency cholecystectomy was performed under the impression of gallbladder empyema. Liver metastasis was found at 7 months postoperatively and the patient expired 9 months after the surgery. At the time of cholecystectomy, the gallbladder showed a necrotic serosal surface with an irregular thickened wall. A mass, 6 cm in length and 3 cm in width, encircled the whole wall of the neck and upper body of the gallbladder. Microscopic findings revealed frequent mitotic figures (more than 20/50 HPF) and tumor necrosis. Hyperchromatic, pleomorphic and spindle shaped neoplastic cells that were arranged in a pattern of short fascicles infiltrated the entire layer of the gallbladder. The tumor cells were immunoreactive for CD117 antigen (c-kit protein) and vimentin. They were negative for desmin, smooth muscle actin and S-100 protein. Mutations of the c-kit proto-oncogene were not found in this case. These findings were sufficient to provide enough clinical, histopathological and immunohistochemical evidence in diagnosing our case as a malignant GIST.

Inhibitor of DNA binding/differentiation helix-loop-helix proteins mediate bone morphogenetic protein-induced osteoblast differentiation of mesenchymal stem cells.

Bone morphogenetic proteins (BMPs) belong to the TGF-beta superfamily and play an important role in development and in many cellular processes. We have found that BMP-2, BMP-6, and BMP-9 induce the most potent osteogenic differentiation of mesenchymal stem cells. Expression profiling analysis has revealed that the Inhibitors of DNA binding/differentiation (Id)-1, Id-2, and Id-3 are among the most significantly up-regulated genes upon BMP-2, BMP-6, or BMP-9 stimulation. Here, we sought to determine the functional role of these Id proteins in BMP-induced osteoblast differentiation. We demonstrated that the expression of Id-1, Id-2, and Id-3 genes was significantly induced at the early stage of BMP-9 stimulation and returned to basal levels at 3 days after stimulation. RNA interference-mediated knockdown of Id expression significantly diminished the BMP-9-induced osteogenic differentiation of mesenchymal progenitor cells. Surprisingly, a constitutive overexpression of these Id genes also inhibited osteoblast differentiation initiated by BMP-9. Furthermore, we demonstrated that BMP-9-regulated Id expression is Smad4-dependent. Overexpression of the three Id genes was shown to promote cell proliferation that was coupled with an inhibition of osteogenic differentiation. Thus, our findings suggest that the Id helix-loop-helix proteins may play an important role in promoting the proliferation of early osteoblast progenitor cells and that Id expression must be down-regulated during the terminal differentiation of committed osteoblasts, suggesting that a balanced regulation of Id expression may be critical to BMP-induced osteoblast lineage-specific differentiation of mesenchymal stem cells.