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Objective Weakness of the hand is a major impairment which limits independent living. Neuromuscular electrical stimulation (NMES) is a common approach to help restore muscle strength. Traditional NMES directly over the muscle often leads to a rapid onset of muscle fatigue. In this study, we investigated the force sustainability of finger flexor muscles using a transcutaneous nerve stimulation approach. Approach Finger flexion forces and high-density electromyogram (HD EMG) signals were obtained while electrical stimulation was applied to the ulnar and median nerve bundles through a stimulation grid on the proximal arm segment. Stimulation was also applied to the finger flexor muscle belly targeting the motor point, serving as a control condition. The force produced from the two stimulation approaches were initially matched, and muscle fatigue was subsequently induced with 5 min of continuous stimulation. The rate of decay of the force and EMG amplitude were quantified, and the spatial distribution of the muscle activation during the sustained contraction was also evaluated. Main results The proximal nerve stimulation approach induced a slower decay in both force and EMG, compared with the stimulation at the motor point. The spatial distribution of the elicited muscle activation showed that the proximal nerve stimulation led to a distributed activation across the intrinsic and extrinsic finger flexor muscles and also activated a wider area within the extrinsic muscle. Significance Our findings demonstrated that the stimulation of the proximal nerve bundles can elicit sustained force output and delayed decrease in the rate of force decline. This is potentially due to a spatially distributed activation of the muscle fibers, compared with the traditional motor point stimulation. Future development of our nerve stimulation approach may enable prolonged usage during rehabilitation or assistance for better functional outcomes.

Carrier is considered a good tool for process warpage control in wafer/panel level packaging technology. Glass is the most common carrier material. Its rigid, strong property makes it have the high potential for recycle in assembly. And its adjustable CTE (coefficient of thermal expansion) also have the advantage for warpage control. Thus glass strength and warpage must be investigated for the developing advanced technology, such as panel level fan-out package. Glass is tested by 4PB (4-point bending) which follows ASTM C158-02 to come out strength. Two kinds of standard glass sample (around 50×50 mm2) are chosen to compare with glass supplier’s datasheet for benchmark. The standard sample has the same material, dimension and test condition with supplier. 3 types of standard glass sample with different CTE are tested for strength. Those samples have similar average strength and strength range. Two kinds of panel glass (300×300 mm2) with different CTE are tested by 4PB to benchmark with standard sample using the same material. The panel glass strength is within the database of standard sample. For 12″ wafer glass, there is no equation to transfer breaking load into glass strength. A standard glass is chosen as the base to build modeling, so that the wafer load can be converted into strength by simulation. And the simulation by finite element method result shows a liner relationship between load and strength which is the same with strength equation from ASTM. Three dimensional digital image correlation (3D-DIC) theory developed equipment named aMA (advanced metrology analyzer) is used for warpage measurement. For standard sample, its warpage is very small, approximately 6 um. But warpage of wafer, panel glass are much bigger than standard sample due to those large sizes. 12″ wafer glass samples, CTE ranges from 3.0 to 8.7, have similar warpage behavior, and the CTE can also be calculated by aMA. The CTE from aMA is similar with that from datasheet. For A-supplier 12″ wafer glass, it shows a saddle warpage shape if the glass is attached a PI film. For B-supplier 12″ wafer glass, the warpage becomes much large if the glass CTE is large than 9.6. And the warpage shape behaves a concentric circle. To control process warpage, glass is added some material such as PI film and jig. The glass with PI film or jig also shows a concentric circle warpage shape at 30°C.

In recent years, Fan-Out (FO) packages have become widely used in handheld, mobile consumer and internet of things (IoT) devices. FO packaging enables a greater I/O density as well as multiple components in the same package. Several types of FO packaging are offered in the market today, for example; embedded wafer level BGA (eWLB), M-Series™ as well as a flip chip based structure referred to as Fan-out Chip-Last Package (FOCLP) The work compares the mechanical and thermal performance of the three types of FO packages. Finite element analyses were carried out to examine mechanical performance metrics, including warpage, stress in the extreme low-k (ELK) interconnect and board level solder joint reliability. Thermal simulations were completed to compare the thermal dissipation differences among the FO package types. The paper concludes with a summary of the advantages and disadvantages of the different FO structures studied.

Real-world stressors are complex and multimodal, involving physical, psychological, and social dimensions. However, the brain networks that mediate stress responses to these stimuli need to be further studied. We used c-Fos mapping in mice to characterize brain circuits activated by exposure to a single episode of multimodal stress (MMS), and compared these to circuits activated by electric foot shocks (EFS). We focused on characterizing c-Fos activity in stress-relevant brain regions including the paraventricular nucleus (PVN) of the hypothalamus and the bed nucleus of the stria terminalis (BNST). We also assessed stress-induced activation of CRH-positive neurons in each of these structures. MMS and EFS activated an overlapping network of brain regions with a similar time course. c-Fos expression within the PVN and the BNST peaked 30–60 min after exposure to both MMS and EFS, and returned to baseline levels within 24 h. Quantification of c-Fos expression within BNST subregions revealed that while c-Fos expression peaked in all subregions 30–60 min after MMS and EFS exposure, the neuronal density of c-Fos expression was significantly higher in the dorsomedial and ventral BNST relative to the dorsolateral BNST. Our preliminary assessment indicated that a great majority of MMS or EFS-activated neurons in the PVN were CRH-positive (>87%); in contrast, about 6–35% of activated neurons in the BNST were CRH-positive. Our findings indicate that both MMS and EFS are effective at activating stress-relevant brain areas and support the use of MMS as an effective approach for studying multidimensional stress in animal models. The results also reveal that the PVN and BNST are part of a common neural circuit substrate involved in neural processing related to stress. Keywords: Multimodal stress, c-Fos, BNST, PVN, CRH

Drop test for solder joint reliability is critical for all area arrays and perimeter-leaded surface mount semiconductor devices typically used in handheld electronic products. Joint Electron Device Engineering Council, JEDEC, published a new test standard, JESD22-B111A, to be the revision of the JESD22-B111 for board level drop test in November, 2016. The major differences between JESD22-B111 and JESD22-B111A are PCB size (132×77mm2 to 77×77mm2), PCB layers (8 layers to 10 layers), sample size (15 components/PCB with package size ≦ 15×15 mm2 to 4 components/PCB with package size ≦ 17×17 mm2) and total number of test components (120 components to 48 components). JESD22-B111A also adds the specifications of PCB pad and solder mask opening size for 0.4mm component pitch and 5 lb-in torque value. The component placement on the square board that defined in JESD22-B111A is symmetric so that all of them shall have same stress level during drop test, it is different from the component placement on the rectangular board that defined in JESD22-B111 which results several stress level during drop test. In this paper, board level drop test and simulation followed JESD22-B111 and JESD22-B111A are executed. The simulation result shows conditions follow JESD22-B111A has both smaller normal stress and plastic strain than conditions follow JESD22-B111; drop test experiment result shows JESD22-B111A has longer characteristic life, too. The study of package surface mount placement orientation for rectangular package under JESD22-B111A condition is also executed by simulation, due to it is not defined in the new revised standard. The simulation result shows circumferential oriented component placement has larger plastic strain and radial oriented component placement has larger normal stress, it means the former ease to have solder fracturing failure mode and the latter ease to have intermetallic compound layers fracturing failure mode.

OBJECTIVE We reduced the computed tomography (CT)-reconstructed field of view (FOV), increasing pixel density across airway structures and reducing partial volume effects, to determine whether this would improve accuracy of airway wall thickness quantification. METHODS We performed CT imaging on a lung phantom and 29 participants. Images were reconstructed at 30-, 15-, and 10-cm FOV using a medium-smooth kernel. Cross-sectional airway dimensions were compared at each FOV with repeated-measures analysis of variance. RESULTS Phantom measurements were more accurate when FOV decreased from 30 to 15 cm (P < 0.05). Decreasing FOV further to 10 cm did not significantly improve accuracy. Human airway measurements similarly decreased by decreasing FOV (P < 0.001). Percent changes in all measurements when reducing FOV from 30 to 15 cm were less than 3%. CONCLUSIONS Airway measurements at 30-cm FOV are near the limits of CT resolution using a medium-smooth kernel. Reducing reconstructed FOV would minimally increase sensitivity to detect differences in airway dimensions.

Smaller form factor, thermal/electrical efficiency and low-cost manufacturing are characteristics of the wafer level chip scale package (WLCSP) which had been widely used by market demand especially in handheld and portable applications in past several years. However, the challenge of board level reliability tests such as drop test, thermal cycling loading test to limit package size for higher I/O density application. Fan-out (FO) technique is developed to broaden the package area and to accommodate an increasing I/O density. The molding dies into an architectural wafer with epoxy molding compound (EMC) by re-constitution (Recon) process. In this study, three-dimensional computational aWLP (advanced wafer level package) model was developed for analyze solder joint reliability during TCoB (thermal cycles on board) testing. Structural factors of thickness of package and dielectric, size of die and package were selected to evaluate correlation with solder joint reliability. The result predicted by finite-element model (FEM) indicated that the lower package flexural rigidity (thinner package), smaller die size, stress buffer enhancement (thicker dielectric thickness), and larger package size would be enhance solder thermal cycling reliability. Examining the effect of each control factor, we notice that the ratio of die size over package size is the most important control factor.

The following essay takes a macro-perspective on the Shishuo xinyu, reading it not in terms of anecdotal narrative or characterological analysis, but through questions of information management and computer-based visualization. We discuss the history of data visualization and seek to demonstrate the interpretive power (and limitations) that such computational methodologies bring to the study of premodern texts. In particular, we are concerned with the use of geographical information systems (GIS) and social network analysis, as well as with how these tools help us to visualize the complex data contained within the text. In many ways, this essay is intended as an introduction to certain aspects of the emerging field of digital humanities, one that simultaneously seeks to show how these new methodologies work within the disciplinary contexts of premodern Chinese cultural studies.

Background As resident “index” procedures change in volume due to advances in technology or reliance on simulation, it may be difficult to ensure trainees meet case requirements. Training programs are in need of metrics to determine how many residents their institutional volume can support. Objective As a case study of how such metrics can be applied, we evaluated a case distribution simulation model to examine program-level mediastinoscopy and endobronchial ultrasound (EBUS) volumes needed to train thoracic surgery residents. Methods A computer model was created to simulate case distribution based on annual case volume, number of trainees, and rotation length. Single institutional case volume data (2011–2013) were applied, and 10 000 simulation years were run to predict the likelihood (95% confidence interval) of all residents (4 trainees) achieving board requirements for operative volume during a 2-year program. Results The mean annual mediastinoscopy volume was 43. In a simulation of pre-2012 board requirements (thoracic pathway, 25; cardiac pathway, 10), there was a 6% probability of all 4 residents meeting requirements. Under post-2012 requirements (thoracic, 15; cardiac, 10), however, the likelihood increased to 88%. When EBUS volume (mean 19 cases per year) was concurrently evaluated in the post-2012 era (thoracic, 10; cardiac, 0), the likelihood of all 4 residents meeting case requirements was only 23%. Conclusions This model provides a metric to predict the probability of residents meeting case requirements in an era of changing volume by accounting for unpredictable and inequitable case distribution. It could be applied across operations, procedures, or disease diagnoses and may be particularly useful in developing resident curricula and schedules.

Wafer Level Chip Scale Package (WLCSP) has been widely used in MEMS and SiP packages; application of mobile and consuming products. It advantages in lightweight, reducing manufacturing cost, low I/O density and high performance because the bumps directly interconnect between die and motherboard. However, the lower Temperature Cycling on Board (TCoB) reliability performances because of CTE mismatches between die and test board was more and more serious for increasing WLCSP package size, especially the size is larger than 6mm × 6mm, the first failure temperature cycle count will below 600 cycles. In this study, both experimental method and Finite Element Method (FEM) simulation will be used to enhance large size WLCSP performance in TCoB reliability test. We will analyze WLCSP structure with Bump Support Film (BSF) to find out the optimum thickness in stress viewpoint by FEM simulation, the board level experiment result and failure phenomenon will be figured out as well.

Reay's relaxed Tverberg conjecture and Conway's thrackle conjecture are open problems about the geometry of pairwise intersections. Reay asked for the minimum number of points in Euclidean d-space that guarantees any such point set admits a partition into r parts, any k of whose convex hulls intersect. Here we give new and improved lower bounds for this number, which Reay conjectured to be independent of k. We prove a colored version of Reay's conjecture for k sufficiently large, but nevertheless k independent of dimension d. Requiring convex hulls to intersect pairwise severely restricts combinatorics. This is a higher-dimensional analog of Conway's thrackle conjecture or its linear special case. We thus study convex-geometric and higher-dimensional analogs of the thrackle conjecture alongside Reay's problem and conjecture (and prove in two special cases) that the number of convex sets in the plane is bounded by the total number of vertices they involve whenever there exists a transversal set for their pairwise intersections. We thus isolate a geometric property that leads to bounds as in the thrackle conjecture. We also establish tight bounds for the number of facets of higher-dimensional analogs of linear thrackles and conjecture their continuous generalizations., 10 pages

This study describes the synthesis of deuterium-labelled fosamprenavir calcium. The stable isotopic-labelled compound was prepared starting from L-phenylalanine in 18 steps with a 9% overall yield. Copyright © 2010 John Wiley & Sons, Ltd.

A 4K×2K H.265/HEVC video codec chip is fabricated in a 28nm CMOS process with a core area of 2.16mm2. This LSI chip integrates a dual-standard (H.265 and H.264) video codec and a series of prevalent (VC-1, WMV-7/8/9, VP-6/8, AVS, RM-8/9/10, MPEG-2/4) decoders into a single chip. It contains 3,558K logic gates and 308KB of internal SRAM. Moreover, it simplifies intra/inter-rate-distortion optimization (RDO) processes and reduces external bandwidth via line-store SRAM pool (LSSP) and data-bus translation (DBT) techniques. For smartphone applications, it completes real-time HEVC encoding and decoding with 4096×2160 resolution and 30fps, and consumes 126.73mW (0.5nJ/pixel) of core power dissipation at 0.9V, at 494MHz (encoding) and 350MHz (decoding). 1080HD and 720HD resolutions are reported as well. The chip features are summarized in Fig. 18.6.1.

We developed a high-precision high-throughput live-cell assay to screen for small molecules that activate the non-muscle sarco/endo-plasmic reticulum calcium ATPase (SERCA2b) using a “2-color” SERCA2b biosensor and a fluorescence-lifetime plate reader (FLT-PR). The 2-color SERCA2b (h2CS2b) biosensor was derived from a human pancreatic SERCA isoform, in which red fluorescent protein (mRuby2) was fused to the N terminus and green fluorescent protein (Clover) to an interior loop. A HEK cell line expressing the h2CS2b biosensors maintained stable expression level of the biosensors for several tens of passages, ideal for large scale HTS campaigns. This biosensor, upon binding of SERCA2b effectors, translates the minute SERCA structural rearrangements into small changes of intramolecular FRET that can only be reliably detected using fluorescence lifetime (FLT). The h2CS2b biosensor provided dose-dependent FRET changes in response to SERCA inhibitors such as thapsigargin, CPA, and BHQ, and SERCA activators previously discovered in this lab. Two instruments developed by Fluorescence Innovations were crucial for this work: a FLT plate reader, which provides a 30-fold increase of precision compared to conventional intensity-based instruments, and a high-speed fluorescence-spectra plate reader, which was used to filter out artifacts due to compound fluorescence. We screened a commercial chemical library of 50000 compounds and identified 94 compounds that significantly affect 2-color SERCA fluorescence lifetime. Functional assays are underway to evaluate the biochemical properties of these small molecules, and their potential for therapeutic application in diabetes and heart failure. This type of assay is being applied to several other drug targets, with promising results. This work was funded by NIH grants to DDT (R01 GM27906, P30 AR0507220), and to GDG (STTR,5R41DA037622-02).

Introduction Work-hour restrictions have decreased flexibility in scheduling and reduced exposure to certain operative cases. These restrictions may affect a resident's ability to meet certification requirements, particularly for rare, unscheduled cases (e.g., cardiothoracic transplants). We developed a computer-based simulation model using variables such as case volume and program size to demonstrate the influence of these factors on the likelihood of certifying a set of residents on rare cases. Methods We built a simulator to predict the probability of attaining certification for surgical residents, using cardiothoracic transplants as a test case. Inputs to the model included operating times, call schedules, and procurement travel times, as well as information on the distribution of times between transplants. Results We simulated 100 years of schedules using our current system parameters of an average of 33 heart and 31 lung transplants per year, and assuming an Accreditation Council for Graduate Medical Education–compliant daily-rotating call schedule. Despite having enough transplants to certify all residents for lungs if all opportunities were distributed equally among residents, the certification rate achieved when constrained by arrival time (and call schedules) and work restrictions was only 55%. Our calculations show that meeting minimum transplant-certification requirements for all residents would require at least 1.5 times the expected number of annual transplants. Conclusions Our model enables analysis of a given program's ability to certify its residents based on program size and volume. These results could be used to design alternative scheduling paradigms to improve certification rates, without requiring reductions in certification requirements or program size.

Background Certain operative cases occur unpredictably and/or have long operative times, creating a conflict between Accreditation Council for Graduate Medical Education (ACGME) rules and adequate training experience. Methods A ProModel-based simulation was developed based on historical data. Probabilistic distributions of operative time calculated and combined with an ACGME compliant call schedule. Results For the advanced surgical cases modeled (cardiothoracic transplants), 80-hour violations were 6.07% and the minimum number of days off was violated 22.50%. There was a 36% chance of failure to fulfill any (either heart or lung) minimum case requirement despite adequate volume. Conclusions The variable nature of emergency cases inevitably leads to work hour violations under ACGME regulations. Unpredictable cases mandate higher operative volume to ensure achievement of adequate caseloads. Publically available simulation technology provides a valuable avenue to identify adequacy of case volumes for trainees in both the elective and emergency setting.

Hematopoietic stem cells (HSCs) reside in the bone marrow in specific niches at the border between bone cells and the bone marrow (endosteal niche) or around blood vessels (perivascular niche). In the endosteal niche, HSCs are maintained at low oxygen levels in a quiescent (dormant) state by adhesion to niche cells. We have previously shown that Gfi1b restricts the expansion and proliferation of HSCs as well as their mobilization or re-localization into peripheral blood. We have proposed that Gfi1b exerts this function by regulating the expression of surface molecules such as integrins on HSCs that are required to maintain them in their bone marrow niche at a quiescent state. The objective of this study was to gain more insight into the precise molecular mechanisms by which Gfi1b regulates HSCs dormancy and mobilization and to obtain insights that may be exploited in the future to improve stem cell therapies or the expansion of human hematopoietic stem cells for clinical use. Immune precipitation and mass spectrometry identified a series of Gfi1b interacting proteins, most notably a group of regulators of the canonical Wnt/beta-catenin pathway. Independent protein IP validation of these findings suggested that Gfi1b can interact with several inhibitors of the canonical Wnt/beta catenin pathway namely with APC (Adenomatous polyposis coli) a tumor suppressor protein and important factor in the beta-catenin destruction complex, with the DNA helicase and chromatin remodeling factor CHD8, which silences beta catenin mediated transcription, with CtBP which antagonizes beta-catenin activity and is part of the LSD1/CoRest histone demethylase complex and with the direct beta-catenin inhibitors TLE1 and TLE3 (also called Groucho). Of particular interest was that the interactions between the Groucho proteins and Gfi1b were dependent on a previously unidentified Groucho binding domain (GBD) in Gfi1b. This is a well-conserved six-amino acid stretch that is found in the middle part of the Gfi1b protein. In addition, the binding of CtBP was dependent on the presence of the 20 amino acid N-terminal SNAG domain in Gfi1b that also mediates LSD1 binding. Using luciferase reporter gene assays (TOP/FOP reporter assay), we found that Gfi1b was able to significantly up-regulates TCF/beta-catenin-dependent transcription upon activation by LiCl or Wnt3A in HEK293 cells. This activity of Gfi1b was dependent on both the presence of the SNAG domain and the newly identified Groucho binding domain. Also, Gfi1b was able to reverse partially the inhibitory effect of CtBP and TLE3 on beta-catenin activity in the TOP/FOP reporter assays. To obtain further evidence that Gfi1b is indeed implicated in regulating the Wnt/beta catenin signaling pathway in hematopoietic stem cells, we FACS sorted Lin-Kit1+Sca+ hematopoietic progenitors (LSK cells) from wt and Gfi1b deficient mice and tested them for expression of Wnt effector genes using a Wnt signaling specific PCR array. We observed that the majority of Wnt target genes were significantly down regulated in Gfi1 deficient LSKs compared to wt LSKs. Among the genes affected the most were typical Wnt targets such as Axin2, Frz7, Tcf4, Klf5, Vegfa and Ccnd1. To show that Gfi1b is able to regulate Wnt pathway effectors in vivo in HSCs, we crossed Gfi1b flox/flox, Mx-Cre mice with animals that carry a NLS-lacZ reporter gene under the control of the endogenous Axin2 promoter/enhancer region. Treatment with pIpC, which deletes Gfi1b correlated with a significant decrease of Axin2 expression in HSCs and MPP1, which are high Gfi1b expressing cells. The Axin2 reporter was not affected by Gfi1b deletion in MPP2 or GMPs, which express low levels or no Gfi1b. The canonical Wnt/b-catenin signaling pathway is recognized as one of the elements that are critically important in the regulation of HSC function. Here we have identified Gfi1b as a potential new player in the Wnt-beta catenin signaling pathway. Our data suggest that Gfi1b acts on at least two inhibitory complexes of this pathway, on the TLE family of Groucho proteins and the CtBP/LSD1 complex and regulates effectors of the Wnt/beta-catenin signaling cascade. We propose therefore that Gfi1b may titer the level of activation of the Wnt/beta-catenin signaling pathway in HSCs, which offers an explanation of the hematopoietic stem cell phenotype seen in mice lacking Gfi1b. Disclosures: No relevant conflicts of interest to declare.