Investigating industry 4.0 technologies in logistics 4.0 usage towards sustainable manufacturing supply chain.

In the era of Industry 4.0 (I4.0), automation and data analysis have undergone significant advancements, greatly impacting production management and operations management. Technologies such as the Internet of Things (IoT), robotics, cloud computing (CC), and big data, have played a crucial role in shaping Logistics 4.0 (L4.0) and improving the efficiency of the manufacturing supply chain (SC), ultimately contributing to sustainability goals. The present research investigates the role of I4.0 technologies within the framework of the extended theory of planned behavior (ETPB). The research explores various variables including subjective norms, attitude, perceived behavior control, leading to word-of-mouth, and purchase intention. By modeling these variables, the study aims to understand the influence of I4.0 technologies on L4.0 to establish a sustainable manufacturing SC. A questionnaire was administered to gather input from small and medium-sized firms (SMEs) in the manufacturing industry. An empirical study along with partial least squares structural equation modeling (SEM), was conducted to analyze the data. The findings indicate that the use of I4.0 technology in L4.0 influences subjective norms, which subsequently influence attitudes and personal behavior control. This, in turn, leads to word-of-mouth and purchase intention. The results provide valuable insights for shippers and logistics service providers empowering them to enhance their performance and contribute to achieving sustainability objectives. Consequently, this study contributes to promoting sustainability in the manufacturing SC by stimulating the adoption of I4.0 technologies in L4.0.

Analysis of thermal decomposition kinetics of chicken feather fiber reinforced Poly-lactic acid composites filament.

Derivative Thermogravimetric analysis under air was used to observe the thermal decomposition process of Chicken feather fiber (CFF) reinforced Poly-lactic acid (PLA) composite filament of 2.2 mm diameter. The thermal degradation of the sample was initiated at 140 Ö¯C. Approximately 75 % of the thermal degradation occurred between the temperature of 357 Ö¯C and 399 Ö¯C. The composite's activation energy was established using the Coats-Redfern method. The results showed that the activation energy of 112.06 kJ/mol is utilized for the sample throughout the temperature range of 23 Ö¯C to 398 Ö¯C. A low activation energy is indicative of rapid chemical reactions between the CFF and PLA molecules. The results from TGA and DTGA indicate that the addition of CFF in the PLA matrix enhanced the thermal stability.

Current biomarkers and treatment strategies in Alzheimer disease: An overview and future perspectives.

Alzheimer's disease (AD), a progressive degenerative disorder first identified by Alois Alzheimer in 1907, poses a significant public health challenge. Despite its prevalence and impact, there is currently no definitive ante mortem diagnosis for AD pathogenesis. By 2050, the United States may face a staggering 13.8 million AD patients. This review provides a concise summary of current AD biomarkers, available treatments, and potential future therapeutic approaches. The review begins by outlining existing drug targets and mechanisms in AD, along with a discussion of current treatment options. We explore various approaches targeting Amyloid ß (Aß), Tau Protein aggregation, Tau Kinases, Glycogen Synthase kinase-3ß, CDK-5 inhibitors, Heat Shock Proteins (HSP), oxidative stress, inflammation, metals, Apolipoprotein E (ApoE) modulators, and Notch signaling. Additionally, we examine the historical use of Estradiol (E2) as an AD therapy, as well as the outcomes of Randomized Controlled Trials (RCTs) that evaluated antioxidants (e.g., vitamin E) and omega-3 polyunsaturated fatty acids as alternative treatment options. Notably, positive effects of docosahexaenoic acid nutriment in older adults with cognitive impairment or AD are highlighted. Furthermore, this review offers insights into ongoing clinical trials and potential therapies, shedding light on the dynamic research landscape in AD treatment.

AI-Assisted Screening of Oral Potentially Malignant Disorders Using Smartphone-Based Photographic Images.

The prevalence of oral potentially malignant disorders (OPMDs) and oral cancer is surging in low- and middle-income countries. A lack of resources for population screening in remote locations delays the detection of these lesions in the early stages and contributes to higher mortality and a poor quality of life. Digital imaging and artificial intelligence (AI) are promising tools for cancer screening. This study aimed to evaluate the utility of AI-based techniques for detecting OPMDs in the Indian population using photographic images of oral cavities captured using a smartphone. A dataset comprising 1120 suspicious and 1058 non-suspicious oral cavity photographic images taken by trained front-line healthcare workers (FHWs) was used for evaluating the performance of different deep learning models based on convolution (DenseNets) and Transformer (Swin) architectures. The best-performing model was also tested on an additional independent test set comprising 440 photographic images taken by untrained FHWs (set I). DenseNet201 and Swin Transformer (base) models show high classification performance with an F1-score of 0.84 (CI 0.79-0.89) and 0.83 (CI 0.78-0.88) on the internal test set, respectively. However, the performance of models decreases on test set I, which has considerable variation in the image quality, with the best F1-score of 0.73 (CI 0.67-0.78) obtained using DenseNet201. The proposed AI model has the potential to identify suspicious and non-suspicious oral lesions using photographic images. This simplified image-based AI solution can assist in screening, early detection, and prompt referral for OPMDs.

Antecedents for online food delivery platform leading to continuance usage intention via e-word-of-mouth review adoption.

The focus of hospitality initially was on ambience and novelty to attract customers. With the rise of the digital revolution, the hospitality industry has also undergone significant change. Long-distance travel at the workplace, odd working hours, and a variety of food options have driven people staying in Indian metropolises towards online food delivery (OFD) services. The popularity of OFD services has risen because of their practicality, simplicity, and a rise in consumer confidence in digital payments. Specifically, for the food industry, digitalization has opened new horizons to capture customers. The competition is not among the big brands, but big brands are competing with homemakers who run tiffin services, and street food hawkers who claim to provide traditional Dhaba-style food and fast food. The customers are loaded with unlimited options to choose the food in terms of price, cuisine, quality, etc. The present research examines the associations between service quality of OFD services, perceived ease of use, and word-of-mouth review adoption, leading to expectation confirmation modeling. The path analysis was carried out using data from 500 Indian respondents residing in Tier-I cities who have been using OFD services regularly. The research outcome shows that servqual has a positive influence on perceived ease of use and confirmation. Additionally, it encourages continued usage intentions because of its favorable impact on the adoption of e-word-of-mouth reviews.

Caroli's Disease Associated with Autosomal Dominant Polycystic Kidney Disease with Acute Pancreatitis: A Case Report.

A rare congenital hepatobiliary disorder called Caroli's disease is characterized by multifocal segmental dilatation of intrahepatic bile ducts that can affect the entire liver or only specific areas of it. Coexisting conditions with Caroli's disease include autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD). ADPKD results in the development of cysts, which are tiny fluid-filled sacs, in the kidneys. Caroli's disease is considered a rare disorder, affecting a small number of individuals worldwide. The symptoms of Caroli's disease can vary from person to person and it also may overlap with other liver and biliary disorders. As a result, it may be challenging to diagnose and manage the condition due to limited awareness and expertise. Increased awareness, research, and specialized medical care are crucial in improving outcomes for individuals affected by this rare disorder. This study involves the case of a 60- year-old woman presented with abdominal pain, fever, weight loss, and jaundice. Her imaging test endoscopic retrograde cholangiopancreatography (ERCP) signifies Caroli's disease with pancreatic duct (PD) calculi and management involves supportive care with antibiotics. Antibiotics were prescribed to prevent or treat infections such as cholangitis and nutritional supplement was recommended in managing Caroli's disease. The patient underwent pancreatic stent placement and was discharged with regular follow-up. So, this case highlights the clinical and diagnostic aspects to improve disease understanding and the progression of Caroli's illness along with ADPKD.

Experience of Treating COVID-19 With Remdesivir and Convalescent Plasma in a Resource-Limited Setting: A Prospective, Observational Study.

BACKGROUND: Convalescent plasma therapy (CPT) and remdesivir (REM) have been approved for investigational use to treat coronavirus disease 2019 (COVID-19) in Nepal. METHODS: In this prospective, multicentered study, we evaluated the safety and outcomes of treatment with CPT and/or REM in 1315 hospitalized COVID-19 patients over 18 years in 31 hospitals across Nepal. REM was administered to patients with moderate, severe, or life-threatening infection. CPT was administered to patients with severe to life-threatening infections who were at high risk for progression or clinical worsening despite REM. Clinical findings and outcomes were recorded until discharge or death. RESULTS: Patients were classified as having moderate (24.2%), severe (64%), or life-threatening (11.7%) COVID-19 infection. The majority of CPT and CPT + REM recipients had severe to life-threatening infections (CPT 98.3%; CPT + REM 92.1%) and were admitted to the intensive care unit (ICU; CPT 91.8%; CPT + REM 94.6%) compared with those who received REM alone (73.3% and 57.5%, respectively). Of 1083 patients with reported outcomes, 78.4% were discharged and 21.6% died. The discharge rate was 84% for REM (n = 910), 39% for CPT (n = 59), and 54.4% for CPT + REM (n = 114) recipients. In a logistic model comparing death vs discharge and adjusted for age, gender, steroid use, and severity, the predicted margin for discharge was higher for recipients of remdesivir alone (0.82; 95% CI, 0.79-0.84) compared with CPT (0.58; 95% CI, 0.47-0.70) and CPT + REM (0.67; 95% CI, 0.60-0.74) recipients. Adverse events of remdesivir and CPT were reported in <5% of patients. CONCLUSIONS: This study demonstrates a safe rollout of CPT and REM in a resource-limited setting. Remdesivir recipients had less severe infection and better outcomes.ClinicalTrials.gov identifier. NCT04570982.

Roles of the matricellular protein Tenascin-C in T-lymphocyte trafficking and etiopathogenesis of Oral Lichen Planus.

OBJECTIVE: This study was aimed at examining the role of Tenascin-C in T cell trafficking in Oral Lichen Planus (OLP). DESIGN: For the in vivo immunohistochemical analyses, 115 OLP samples were collected from patients and immunostaining was performed. The intensity and distribution of TN-C expression were quantified and correlated with histological analyses of basement membrane integrity and presence of inflammatory infiltrate. For the in vitro study, TN-C and collagen were coated on culture plates and migration of T lymphocytes was assessed. RESULTS: TN-C immunoexpression was increased in terms of both distribution and intensity along the basement membrane zone. These changes were significantly associated with basement membrane duplication (distribution p < 0.002 and intensity p < 0.001) and bands of inflammation (distribution p < 0.002 and intensity p < 0.001) assessed by Chi-square test. T lymphocytes demonstrated significant migration towards TN-C as compared to collagen (n = 3, p < 0.05). CONCLUSIONS: These findings indicate TN-C may have a key role in promoting T cell migration at the epithelial-mesenchymal junction in OLP. These observations suggest TN-C could be a good target for therapeutic intervention, either in itself or synergistically with anti-inflammatory directed strategies in this chronic disease management.

Role of immunoreactive patterns of lymph nodes in neck dissection cases of oral squamous cell carcinoma: a clinical and histopathological study.

OBJECTIVES: Metastasis in oral squamous cell carcinoma (OSCC) can occur in a variety of ways, and draining lymphatics and lymph nodes serve as a common route. Prior to metastasis, lymph nodes elicit an immune response to either wall off or create a favorable environment for homing of tumor cells. This immune response to tumor stimuli is visualized by recognizing various immunoreactive patterns exhibited by the lymph node. The present study aims to evaluate the role of immuno-morphologic patterns of the lymph node in neck dissection for cases of OSCC. MATERIALS AND METHODS: Our retrospective study included 50 neck dissection cases of OSCC and a total of 1,078 lymph nodes. The grades of primary tumors with eight different immunoreactive patterns were compared. Vascularity and metastasis in lymph nodes were also evaluated. RESULTS: The lymphocyte predominant pattern was the most common immunoreactive pattern found in 396 of 1,078 lymph nodes. Patterns of lymphocyte predominant (P=0.0005), sinus histiocytosis (P=0.0500), paracortical hyperplasia (P=0.0001), cortical hyperplasia (P=0.0001), and increased vascularity (P=0.0190) were significantly associated with tumor grade. CONCLUSION: The present study adds to the understanding of lymph node immunoreactivity patterns and their correlation with tumor grade. We recommend further study of lymph node patterns for all sentinel lymph node biopsies and routine neck dissections for OSCCs.

Assessment of cell block technique in head and neck pathology diagnoses: A preliminary study.

OBJECTIVE: The head and neck region is a composite site made of multiple tissue components. These tissues when affected by disease or pathology present with an array of changes in the tissue architecture and pattern. It is essential to visualize the cellular details and tissue patterns for accurate diagnosis and treatment planning. Aspiration cytology primarily makes use of the cellular details for diagnosing lesions of the head and neck. Despite the promising results, its use is still limited in certain cases of the head and neck. The reason implicated could be the indiscernible appearance of cells in the absence of tissue integrity. In this regard, cell blocks are known to facilitate the visualization of the cytomorphological as well as the tissue arrangement patterns. Thus, the present study was designed to evaluate the role of cell block cytology in the diagnosis of various lesions of the head and neck. METHODS: Odontogenic lesions, epithelial carcinomas and connective tissue pathology of the head and neck origin were included in the study (n = 45). Aspiration cytology smears and cell block diagnosis were compared with tissue biopsy diagnosis for determining their sensitivity (%) and diagnostic efficacy. RESULTS: Cell blocks showed distinct preservation of the architectural pattern. In case of fluid-filled lesions, the contents were preserved and correlated with the tissue biopsy results. The results of cell blocks were similar to that of tissue biopsy in majority of the cases (95.56%). CONCLUSION: We recommend using cell blocks as a part of routine laboratory practice for all head-neck cases.

Role of immunoreactive patterns of lymph nodes in neck dissection cases of oral squamous cell carcinoma: a clinical and histopathological study

OBJECTIVES@#Metastasis in oral squamous cell carcinoma (OSCC) can occur in a variety of ways, and draining lymphatics and lymph nodes serve as a common route. Prior to metastasis, lymph nodes elicit an immune response to either wall off or create a favorable environment for homing of tumor cells. This immune response to tumor stimuli is visualized by recognizing various immunoreactive patterns exhibited by the lymph node. The present study aims to evaluate the role of immuno-morphologic patterns of the lymph node in neck dissection for cases of OSCC.@*MATERIALS AND METHODS@#Our retrospective study included 50 neck dissection cases of OSCC and a total of 1,078 lymph nodes. The grades of primary tumors with eight different immunoreactive patterns were compared. Vascularity and metastasis in lymph nodes were also evaluated.@*RESULTS@#The lymphocyte predominant pattern was the most common immunoreactive pattern found in 396 of 1,078 lymph nodes. Patterns of lymphocyte predominant (P=0.0005), sinus histiocytosis (P=0.0500), paracortical hyperplasia (P=0.0001), cortical hyperplasia (P=0.0001), and increased vascularity (P=0.0190) were significantly associated with tumor grade.@*CONCLUSION@#The present study adds to the understanding of lymph node immunoreactivity patterns and their correlation with tumor grade. We recommend further study of lymph node patterns for all sentinel lymph node biopsies and routine neck dissections for OSCCs.

Role of immunoreactive patterns of lymph nodes in neck dissection cases of oral squamous cell carcinoma: a clinical and histopathological study

OBJECTIVES: Metastasis in oral squamous cell carcinoma (OSCC) can occur in a variety of ways, and draining lymphatics and lymph nodes serve as a common route. Prior to metastasis, lymph nodes elicit an immune response to either wall off or create a favorable environment for homing of tumor cells. This immune response to tumor stimuli is visualized by recognizing various immunoreactive patterns exhibited by the lymph node. The present study aims to evaluate the role of immuno-morphologic patterns of the lymph node in neck dissection for cases of OSCC. MATERIALS AND METHODS: Our retrospective study included 50 neck dissection cases of OSCC and a total of 1,078 lymph nodes. The grades of primary tumors with eight different immunoreactive patterns were compared. Vascularity and metastasis in lymph nodes were also evaluated. RESULTS: The lymphocyte predominant pattern was the most common immunoreactive pattern found in 396 of 1,078 lymph nodes. Patterns of lymphocyte predominant (P=0.0005), sinus histiocytosis (P=0.0500), paracortical hyperplasia (P=0.0001), cortical hyperplasia (P=0.0001), and increased vascularity (P=0.0190) were significantly associated with tumor grade. CONCLUSION: The present study adds to the understanding of lymph node immunoreactivity patterns and their correlation with tumor grade. We recommend further study of lymph node patterns for all sentinel lymph node biopsies and routine neck dissections for OSCCs.

Modified Alcohol-Formalin Cell Block Technique in Head and Neck Pathology Diagnosis.

OBJECTIVES: Cell block preparation is a recognized technique in histopathological diagnosis. This technique aids in maintaining an intact architecture and reducing the diagnostic errors associated with fine-needle aspiration cytology. Numerous techniques have been put forth, but the need for an optimal technique for routine use in the laboratory still persists. The aim of our study was to establish a cell block technique which aids in the accurate diagnosis of head and neck pathology. METHODOLOGY: A modified cell block technique was developed using alcohol-formalin as a fixative. Forty fine-needle aspiration fluids from clinically and radiologically diagnosed cases of head and neck pathology were used as samples. The cell block sections were compared with the cytology smears to determine the utility of the technique. RESULTS: The cell blocks presented with better preservation of the architectural framework and enabled a quick diagnosis. Cellular clumping was negligible, and nuclear as well as cellular details were maintained similar to tissue sections. It led to the integration of conventional techniques using 10% neutral buffered formalin with that of the 10% alcohol-formalin technique. CONCLUSION: Modified cell block technique can be used as a simple and effective tool in the routine diagnosis of head and neck pathology.

Immunoexpression of programmed cell death 4 protein in normal oral mucosa, oral epithelial dysplasia and oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the frequently reported cancer of the head and neck. Recent studies are being conducted to evaluate the role of potential markers for diagnosing the stages of development of OSCC from normal cells. AIM: The aim of this study is to evaluate and compare the immunoexpression of programmed cell death 4 (PDCD4) protein in normal oral mucosa, oral epithelial dysplasia (OED) and OSCC. MATERIALS AND METHODS: Histologically diagnosed, formalin-fixed paraffin-embedded archived cases (n = 100) of normal mucosa (n = 10), OED (n = 60) and OSCC (n = 30) were analyzed immunohistochemically in the present retrospective study using monoclonal rabbit antihuman PDCD4. OED and squamous cell carcinoma were graded according to the World Health Organization and Broder's histological grading criteria, respectively. Clinical parameters and immunohistochemical results were analyzed by Fisher exact test using SPSS software. P <0.05 was indicative of significant differences. RESULTS: PDCD4 expression was observed in the normal oral mucosa, OED and OSCC. The maximum expression was observed in the normal oral mucosa, which reduced significantly in OED and OSCC (P = 0.017). With the increase in the transformation from normal cells to cancer cells, a shift from nuclear to cytoplasmic staining was observed indicating predominant cytoplasmic localization of stain as a feature of altered cells. CONCLUSION: The present study delineates the molecular difference between the normal, dysplastic and carcinomatous cells; and points toward the role of PDCD4 localization in the proliferation of cells. This study thus highlights the need for further research with inclusion of long follow-up period and other pathological criteria such as inflammation and microenvironment, immune status of patient and tumor stage, which could aid in the development of prospective diagnostic options.

Prevalence of human papillomavirus infection among women in rural Nepal.

INTRODUCTION: In this study we aimed to determine the overall and type-specific prevalence of cervical human papillomavirus (HPV) infection and risk factors for such infection among women in rural Nepal, and to investigate the distribution of HPV infection by cervical cytology. MATERIAL AND METHODS: The study was conducted among women aged ≥15 years in five rural villages within Kavre District in Nepal. Sociodemographic data and information on risk factors for cervical cancer were obtained through an interview, and a cervical specimen was collected for HPV DNA detection and typing using the Anyplex™ ll HPV28 Detection system, and for Papanicolaou test. RESULTS: Among the 1289 women in whom a valid HPV result was obtained the median age was 40 years (range 17-86 years). Overall, the HPV prevalence was 14.4%, 7.9% for high-risk and 6.5% for low-risk HPV types, and was similar between age groups. The five most common HR types were HPV-18 (2.3%), HPV-51 (1.2%), HPV-59 (1.1%), HPV-31 (0.9%), and HPV-16 (0.8%). The prevalence of high-risk types in women with and without abnormal cytology was 8.3 and 7.7%, respectively. HPV infection was associated with current smoking, formal education, and being married to a husband with at least one previous marriage. CONCLUSIONS: This is the first population-based study to report the prevalence of a broad range of HPV types among women from rural Nepal. These data are crucial for development of preventive strategies to reduce cervical cancer burden in the country.

Analysis of preference for carbon source utilization among three strains of aromatic compounds degrading Pseudomonas.

Soil isolates Pseudomonas putida CSV86, Pseudomonas aeruginosa PP4 and Pseudomonas sp. C5pp degrade naphthalene, phthalate isomers and carbaryl, respectively. Strain CSV86 displayed a diauxic growth pattern on phenylpropanoid compounds (veratraldehyde, ferulic acid, vanillin or vanillic acid) plus glucose with a distinct second lag-phase. The glucose concentration in the medium remained constant with higher cell respiration rates on aromatics and maximum protocatechuate 3,4-dioxygenase activity in the first log-phase, which gradually decreased in the second log-phase with concomitant depletion of the glucose. In strains PP4 and C5pp, growth profile and metabolic studies suggest that glucose is utilized in the first log-phase with the repression of utilization of aromatics (phthalate or carbaryl). All three strains utilize benzoate via the catechol 'ortho' ring-cleavage pathway. On benzoate plus glucose, strain CSV86 showed preference for benzoate over glucose in contrast to strains PP4 and C5pp. Additionally, organic acids like succinate were preferred over aromatics in strains PP4 and C5pp, whereas strain CSV86 co-metabolizes them. Preferential utilization of aromatics over glucose and co-metabolism of organic acids and aromatics are found to be unique properties of P. putida CSV86 as compared with strains PP4 and C5pp and this property of strain CSV86 can be exploited for effective bioremediation.

Helenalin-mediated post-transcriptional regulation of p21(Cip1) inhibits 3T3-L1 preadipocyte proliferation.

We have previously shown that post-transcriptional mechanisms involving the 26S proteasome regulate the cyclin-dependent kinase inhibitors (CKIs), p21(Cip1) and p27(Kip1) during preadipocyte proliferation. Earlier studies further demonstrated that the anti-inflammatory, anti-carcinogenic phytochemical, helenalin is a potent inhibitor of periodic Skp2 accumulation, an F-box protein mediating SCF E3 ligase ubiquitylation and degradation of both CKIs during S phase progression. Data presented here demonstrate that helenalin dose-dependently induced G1 arrest of synchronously replicating 3T3-L1 preadipocytes. This effect occurred in the absence of discernable indices of cell toxicity or apoptosis under the conditions used in this study. Our results demonstrate that helenalin markedly increased p21 protein accumulation in both density-arrested and proliferating preadipocytes in a dose-dependent manner. This increase in p21 protein abundance occurred without change in mRNA transcript demonstrating that post-transcriptional mechanisms were involved. This notion was further supported by the modest accumulation of polyubiquitylated p21 following treatment with helenalin suggesting that suppression of targeted p21 proteolysis by the 26S proteasome contributed to helenalin-mediated p21 accumulation. The increase in p21 protein was compartmentalized to the nucleus where p21 is known to inhibit cell cycle progression. Finally, helenalin increased protein-protein interactions between p21 and cyclin-dependent kinase 2 (Cdk2) which may account in part for the anti-proliferative effect in 3T3-L1 preadipocytes.

Skp2-mediated p27(Kip1) degradation during S/G2 phase progression of adipocyte hyperplasia.

p27(Kip1), an important regulator of Cdk2 activity and G1/S transition, is tightly regulated in a cell-type and condition-specific manner to integrate mitogenic and differentiation signals governing cell cycle progression. We show that p27 protein levels progressively declined from mid-G1 through late-G2 phase as density-arrested 3T3-L1 preadipocytes synchronously reentered the cell cycle during early stages of adipocyte differentiation. This dramatic fall in p27 protein accumulation was due, at least in part, to a decrease in protein stability. Specific inhibitors of the 26S proteasome were shown to completely block the decrease in p27 protein levels throughout G1, increase the abundance of ubiquitylated p27 protein, and inhibit G1/S transition resulting in G1 arrest. It is further demonstrated that p27 was phosphorylated on threonine 187 during S phase progression by Cdk2 and that phosphorylated p27 was polyubiquitylated and degraded. Furthermore, we demonstrate that Skp2 and Cks1 dramatically increased during S/G2 phase progression concomitantly with the maximal fall in p27 protein. Complete knockdown of Skp2 with RNA interference partially prevented p27 degradation equivalent to that observed with Cdk2 blockade suggesting that the SCF(Skp2) E3 ligase and other proteasome-dependent mechanisms contribute to p27 degradation during preadipocyte replication. Interestingly, Skp2-mediated p27 degradation was not essential for G1/S or S/G2 transition as preadipocytes shifted from quiescence to proliferation during adipocyte hyperplasia. Finally, evidence is presented suggesting that elevated p27 protein in the absence of Skp2 was neutralized by sequestration of p27 protein into Cyclin D1/Cdk4 complexes.