Hye-Ran Kim

Impairment of Instrumental Activities of Daily Living in Patients with Mild Cognitive Impairment

Objective This study was conducted to examine the following: whether patients with mild cognitive impairment (MCI) show impairments in instrumental activities of daily living (IADL) as compared to controls; to identify the functional sub-domains of instrumental activities of daily living (IADL) that are affected in MCI and, finally, to identify the Seoul-Instrumental Activities of Daily Living (S-IADL) scale cut-off score that best differentiated between MCI and controls. Methods This study was carried out at the geropsychiatry clinic, university hospital. The study participants included 66 patients with MCI and 61 normal elderly. The S-IADL and Seoul-Activities of Daily Living (S-ADL) scales were administered to the main caregivers of all participants in order to assess everyday functioning. Results The total S-IADL score was significantly higher in the patients with MCI [mean (SD) score=4.47 (2.06)] than in the controls [mean (SD) score=1.44 (1.65)] (p<0.001). The patients with MCI performed significantly worse on IADLs, such as the ability to use the telephone, prepare meals, take medication, manage belongings, keep appointments, talk about recent events, and perform leisure activities/hobbies (p<0.05). The S-IADL scale discriminated well between patients with MCI and controls (Area Under Curve=87%). Conclusion The patients with MCI showed impairments in the ability to perform complex ADL in comparison to healthy controls. IADLs related to memory and frontal/executive functioning were particularly affected in MCI.

A 7 Gb/s/pin 1 Gbit GDDR5 SDRAM With 2.5 ns Bank to Bank Active Time and No Bank Group Restriction

This paper describes a 1 Gbit GDDR5 SDRAM with enhanced bank access flexibility for efficient data transfer in 7 Gb/s per pin IO bandwidth. The enhanced flexibility is achieved by elimination of bank group restriction and reduction of bank to bank active time to 2.5 ns. The effectiveness of these key features is verified by system model simulation including memory and its controller. To realize the enhanced bank access flexibility, this DRAM employs the following techniques: skewed control logic, PVT variation compensated IO sense amplifier with auto calibration by replica impedance monitor, FIFO based BLSA enable signal generator, low latency VPP generator and active jitter canceller. This GDDR5 SDRAM was fabricated in 50 nm standard DRAM process in 61.6 die area and operates with 1.5 V power supply.

A 60nm 6Gb/s/pin GDDR5 Graphics DRAM with Multifaceted Clocking and ISI/SSN-Reduction Techniques

Demand for high-speed DRAM in graphics application pushes a single-ended I/O signaling to operate up to 6Gb/s. To maintain the speed increase, the GDDR5 specification shifts from GDDR3/4 with respect to forwarded clocking, data training for write and read de-skewing, clock training, channel-error detection, bank group and data coding. This work tackles challenges in GDDR5 such as clock jitter and signal integrity.

Serum S100B Levels and Major Depressive Disorder: Its Characteristics and Role in Antidepressant Response.

Objective S100B is a neurotrophic factor that is involved in neuroplasticity. Neuroplasticity is disrupted in depression; however, treatment with antidepressants can restore neuroplasticity. S100B has previously been used as a biological marker for neuropathology and neuroplasticity; therefore, in this study, we compared serum S100B levels in depressive patients to those of normal controls. In addition, we compared the serum S100B levels of antidepressant responders to those of nonresponders. Methods Thirty five normal controls and 59 depressive patients were enrolled in this study. Depressive patients entered a 6 week clinical trial that included treatment with antidepressants. The serum S100B levels and clinical assessments, which included Hamilton depression rating scores, were measured at baseline and after 6 weeks of treatment with antidepressants. The difference in the serum S100B levels between depressive patients and normal controls and between antidepressant responders and nonresponders was then compared. Results There were no significant differences in the serum S100B levels of normal controls and depressive patients. In addition, 30 of the depressive patients responded to antidepressant treatment while 29 did not. Finally, the responders had significantly higher baseline serum S100B levels than the nonresponders. Conclusion The results of this study suggest that the baseline serum S100B level is associated with the subsequent response to antidepressants. In addition, the high baseline serum S100B level that was observed in depressive patients may enhance neuroplasticity, which results in a favorable therapeutic response to antidepressants.

A 40nm 2Gb 7Gb/s/pin GDDR5 SDRAM with a programmable DQ ordering crosstalk equalizer and adjustable clock-tracking BW

Most DRAM interfaces such as GDDR5 and DDR3 use parallel single-ended signaling due to pin-count restriction and backward compatibility. Notwithstanding poor signal and power integrity issues, GDDR5 speed reached beyond 5Gb/s in recent years by utilizing data bus inversion, error-detection coding, data training and channel equalization [1–3]. However, channel crosstalk is becoming a major barrier to further speed improvement. A common solution for channel crosstalk reduction at the system level is to use a shielding line or wide spacing between signal lines, but increasing the number of layers in a chip package and PCB increase system cost. To remove the shielding lines and increase speed, this paper presents a channel crosstalk equalizer with programmable signal ordering capability for the DRAM transmitter. In addition, this paper addresses tri-mode clocking to reduce the system jitter for better timing margin: PLL off, LC-PLL and injection-locked oscillator.

Altered Cell Viability and Proliferation Activity of Peripheral Lymphocytes in Patients with Alzheimer's Disease

Objective We evaluated cell viability and proliferation activity of peripheral lymphocytes as potential models of neuronal death in Alzheimers disease (AD). Methods We analyzed the cell viability and proliferation activity of phytohemagglutinin (PHA)-activated lymphocytes from 68 AD patients and 33 normal controls. The cellular measures were made at baseline (0 hr), 24 hrs, 48 hrs, 72 hrs, and 96 hrs after PHA stimulation. Results Cell viability in the AD patients was significantly decreased at 72 hrs and 96 hrs, compared with the normal controls. The declining ramp of the proliferation activity from 48 hrs to 72 hrs after PHA stimulation was significantly related to cell viability at 72 hrs and at 96 hrs in the AD patients. Conclusion Lymphocytes from patients with AD have altered viability and proliferation characteristics in culture following PHA stimulation. These findings suggest that lymphocytes may be used as a peripheral tissue model of cell cycle dysregulation in AD.

A 3.2 Gbps/pin 8 Gbit 1.0 V LPDDR4 SDRAM With Integrated ECC Engine for Sub-1 V DRAM Core Operation

A 1.0 V 8 Gbit LPDDR4 SDRAM with 3.2 Gbps/pin speed and integrated ECC engine for sub-1 V DRAM core is presented. DRAM internal read-modify-write operation for data masked write makes the integrated ECC engine possible in a commodity DRAM. Time interleaved latency and IO control circuits enable 1.0 V operation at target speed. To reach 3.2 Gbps with improved power efficiency over conventional mobile DRAMs, the following IO features are introduced: Low voltage swing terminated logic drivers with VOH level calibration and periodic ZQ calibration, unmatched DQ/DQS scheme and DQS oscillator for DQS tree delay tracking. This chip is fabricated in 25 nm DRAM process on 88.1 mm 2 die area.

Genetic prediction of antidepressant drug response and nonresponse in Korean patients.

Genetic polymorphism contributes to variation in response to drug treatment of depression. We conducted three independent 6-week treatment studies in outpatients with major depressive disorder (MDD) to develop a pharmacogenomic model predicting response and nonresponse. We screened candidate genomic markers for association with response to selective serotonin reuptake inhibitors (SSRIs). No patients had received any antidepressant drug treatment in the current episode of depression. Outcome evaluation was blinded to drug and genotype data. The prediction model derived from a development sample of 239 completer cases treated with SSRIs comprised haplotypes and polymorphisms related to serotonin synthesis, serotonin transport, glutamate receptors, and GABA synthesis. The model was evaluated prospectively for prediction of outcome in a validation sample of 176 new SSRI-treated completer cases. The model gave a prediction in 60% of these cases. Predictive values were 85% for predicted responders and 86% for predicted nonresponders, compared to prior probabilities of 66% for observed response and 34% for observed nonresponse in those cases (both P<0.001). Convergent cross-validation was obtained through failure of the model to predict outcomes in a third independent sample of 189 completer cases who received non-SSRI antidepressants. We suggest proof of principle for genetic guidance to use or avoid SSRIs in a majority of Korean depressed patients.

Overexpression of Cell Cycle Proteins of Peripheral Lymphocytes in Patients with Alzheimer's Disease.

Objective Biological markers for Alzheimers disease (AD) will help clinicians make objective diagnoses early during the course of dementia. Previous studies have suggested that cell cycle dysregulation begins earlier than the onset of clinical manifestations in AD. Methods We examined the lymphocyte expression of cell cycle proteins in AD patients, dementia controls (DC), and normal controls (NC). One-hundred seventeen subjects (36 AD, 31 DC, and 50 NC) were recruited. The cell cycle proteins CDK2, CDK4, CDK6, cyclin B, and cyclin D were measured in peripheral lymphocytes. Cell cycle protein expression in the three groups was compared after adjusting for age and sex. Results The levels of cell cycle proteins CDK2, CDK4, CDK6, cyclin B, and cyclin D were significantly higher in AD patients than in the NC subjects. The DC group manifested intermediate levels of cell cycle proteins compared with the AD patients and the NC subjects. The present study indicates that cell cycle proteins are upregulated in the peripheral lymphocytes of AD patients. Conclusion Cell cycle dysregulation in peripheral lymphocytes may present a promising starting point for identifying peripheral biomarkers of AD.

G1/S Cell Cycle Checkpoint Defect in Lymphocytes from Patients with Alzheimer's Disease

Objective We compared the cell responsiveness of activated lymphocytes to rapamycin, which blocks the G1/S transition, between patients with Alzheimers disease (AD) and normal controls to assess the early phase control defect in cell cycle. Methods Blood samples of 26 patients with AD and 28 normal controls were collected to separate peripheral lymphocytes. We measured the proportion of each cell cycle phase in activated lymphocytes using flow cytometry and evaluated the responsiveness of these lymphocytes to rapamycin. Results The patients with AD were older than the normal controls (AD 74.03±7.90 yr vs. control 68.28±6.21 yr, p=0.004). The proportion of G1 phase cells in the AD group was significantly lower than that in the control group (70.29±6.32% vs. 76.03±9.05%, p=0.01), and the proportion of S phase cells in the AD group was higher than that in control group (12.45±6.09% vs. 6.03±5.11%, p=0.001). Activated lymphocytes in patients with AD were not arrested in the G1 phase and they progressed to the late phase of the cell cycle despite rapamycin treatment, in contrast to those of normal subjects. Conclusion The patients with AD probably have a control defect of early phase cell cycle in peripheral lymphocytes that may be associated with the underlying pathology of neuronal death.