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The Cu pillar bump to Cu pillar bump bonding process, commonly used in bonding technology for the 3D stacking of TSV (through silicon via) formed chips, requires an additional process for the generation of bumps on the face and back-side of the chip, and it has a drawback in that it is structurally vulnerable to mechanical stresses, such as thermal stress. This study proposes an ISB (insert-bump) bonding process to overcome such drawbacks. Compared to the conventional Cu pillar bump to Cu pillar bump bonding process, the ISB bonding process has advantages in that it is simple and has high mechanical reliability of the package due to the mechanical interlocking. The stress distributions at the joints of the packages produced from Cu pillar bump to Cu pillar bump bonding and ISB processes were compared and analyzed through FEM analyses, and characteristics analyses of the fracture mode and joint characteristics; process variable optimization with respect to the bonding parameters was also conducted through experiments. The results of the analyses and experiments verified that the ISB bonding process yields a bonding strength of 917.6 mgf/bump, which is approximately twice as much as that of the conventional Cu pillar bump to Cu pillar bump bonding, and which yields a highly reliable mechanical structure. [ABSTRACT FROM AUTHOR]

We estimated the genome size of Korean ginseng ( Panax ginsengC.A. Meyer), a medicinal herb, constructed a HindIII BAC library, and analyzed BAC-end sequences to provide an initial characterization of the library. The 1C nuclear DNA content of Korean ginseng was estimated to be 3.33 pg (3.12Ö10 3 Mb). The BAC library consists of 106,368 clones with an average size of 98.61 kb, amounting to 3.34 genome equivalents. Sequencing of 2167 BAC clones generated 2492 BAC-end sequences with an average length of 400 bp. Analysis using BLAST and motif searches revealed that 10.2%, 20.9% and 3.8% of the BAC-end sequences contained protein-coding regions, transposable elements and microsatellites, respectively. A comparison of the functional categories represented by the protein-coding regions found in BAC-end sequences with those of Arabidopsis revealed that proteins pertaining to energy metabolism, subcellular localization, cofactor requirement and transport facilitation were more highly represented in the P. ginseng sample. In addition, a sequence encoding a glucosyltransferase-like protein implicated in the ginsenoside biosynthesis pathway was also found. The majority of the transposable element sequences found belonged to the gypsy type (67.6%), followed by copia (11.7%) and LINE (8.0%) retrotransposons, whereas DNA transposons accounted for only 2.1% of the total in our sequence sample. Higher levels of transposable elements than protein-coding regions suggest that mobile elements have played an important role in the evolution of the genome of Korean ginseng, and contributed significantly to its complexity. We also identified 103 microsatellites with 3?38 repeats in their motifs. The BAC library and BAC-end sequences will serve as a useful resource for physical mapping, positional cloning and genome sequencing of P. ginseng. [ABSTRACT FROM AUTHOR]

Background: Socioeconomic variables including race, education, and income have been shown to affect vestibular schwannoma incidence, treatment, and outcomes. We sought to determine the impact of socioeconomic factors on quality of life at the time of vestibular schwannoma diagnosis., Methods: Retrospective cohort study conducted at a tertiary academic center. All patients evaluated for vestibular schwannoma from March 1, 2010 to December 31, 2021 who completed at least one Penn Acoustic Neuroma Quality of Life (PANQOL) questionnaire at presentation or prior to any intervention were included. PANQOL scores were compared across income quintiles, racial groups, and health insurance categories., Results: Two-hundred and ninety-six patients who had non-missing information on variables of interest were included. Compared to White/Caucasian patients (84.5 %), Black/African American patients (4.7 %) had significantly lower PANQOL total scores (b = -12.8[-21.7, -4.0], p = 0.005). Compared to patients with Commercial insurance (53 %), patients who were Uninsured/ Self-pay (1.7 %) had significantly lower PANQOL total scores (b = -16.7[-31.4, -1.9], p = 0.027). Patients in higher income quintiles had significantly higher PANQOL total scores (b = 11.7[3.9, 19.5], p = 0.004 comparing highest income quintile to lowest). After controlling for potential confounders, income quintile (b = 9.6[1.3, 17.9], p = 0.023 comparing highest quintile to lowest) and insurance (b = -17.0[-31.9, -21], p = 0.025 comparing Uninsured/Self-pay to Commercial insurance) remained predictors of total PANQOL score., Conclusions: Socioeconomic factors including race, health insurance, and income appear to contribute to quality of life at the time of vestibular schwannoma diagnosis. These variables are interrelated and the effects of race may be mediated in part by differences in income and health insurance coverage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In Gamma Knife (GK) radiosurgery, dose rate decreases during the life cycle of its radiation source, extending treatment times. Prolonged treatments influence the amount of sublethal radiation injury that is repaired during exposure, and is associated with decreased biologically-equivalent dose (BED). We assessed the impact of treatment times on clinical outcomes following GK of the trigeminal nerve - a rare clinical model to isolate the effects of treatment times. This is a retrospective analysis of 192 patients with facial pain treated across three source exchanges. All patients were treated to 80 Gy with a single isocenter. Treatment time was analyzed in terms of patient anatomy-specific dose rate, as well as BED calculated from individual patient beam-on times. An outcome tool measuring pain in three distinct domains (pain intensity, interference with general and oro-facial activities of daily living), was administered before and after intervention. Multivariate linear regression was performed with dose rate/BED, brainstem dose, sex, age, diagnosis, and prior intervention as predictors. BED was an independent predictor of the degree of improvement in all three dimensions of pain severity. A decrease in dose rate by 1.5 Gy/min corresponded to 31.8% less improvement in the overall severity of pain. Post-radiosurgery incidence of facial numbness was increased for BEDs in the highest quartile. Treatment time is an independent predictor of pain outcomes, suggesting that prescription dose should be customized to ensure iso-effective treatments, while accounting for the possible increase in adverse effects at the highest BEDs., Competing Interests: Authors’ disclosure of potential conflicts of interest The authors have nothing to disclose., (© 2022 Old City Publishing, Inc.)

Background: Short-length stems were developed to reduce bone loss of the proximal femur and potentially decrease the incidence of thigh pain after cementless THA. However, it remains unknown whether short stems indeed reduce bone loss or the frequency of thigh pain., Questions/purposes: Is there a difference between short- and standard-length stems in terms of: (1) the frequency or severity of thigh pain, (2) modified Harris hip scores, (3) implant loosening, or (4) bone mineral density as measured by dual-energy x-ray absorptiometry?, Methods: Between March 2013 and January 2014, three surgeons performed 205 primary THAs. To be eligible, patients needed to be at least 20 years of age, have not undergone previous history of hip surgery, and have no metabolic bone disease. A total of 100 patients were randomized to receive THA either with a short stem (n = 56) or with a standard-length stem (n = 44). Both stems were proximally coated, tapered, cementless stems. Compared with standard stems, short stems typically were 30- to 35-mm shorter. A total of 73% (41 of 56) and 77% (34 of 44) of those groups, respectively, were accounted for at a minimum of 5 years and were analyzed. The presence of thigh pain during activity was evaluated using a 10-point VAS, and the modified Harris hip score was calculated by research assistants who were blinded to the treatment groups. Plain radiographs were taken at 6 weeks, 6 months, and 12 months postoperatively, and every 1 year thereafter; loosening was defined as subsidence > 3 mm or a position change > 3° on serial radiographs. Radiological assessment was performed by two researchers who did not participate in the surgery and follow-up evaluations. Bone mineral density of the proximal femur was measured using dual-energy x-ray absorptiometry at 4 days, 1 year, 2 years, and 5 years postoperatively. The primary endpoint of our study was the incidence of thigh pain during 5-year follow-up. Our study was powered at 80% to detect a 10% difference in the proportion of patients reporting thigh pain at the level of 0.05., Results: With the numbers available, we found no difference between the groups in the proportion of patients with thigh pain; 16% (9 of 56) of patients in the short-stem group and 14% (6 of 44) of patients in the standard-stem group experienced thigh pain during the follow-up period (p = 0.79). In all patients, the pain was mild or moderate (VAS score of 4 or 6 points). Among the 15 available patients who reported thigh pain, there was no difference between the implant groups in mean severity of thigh pain (4.3 ± 0.8 versus 4.2 ± 0.7; p = 0.78). There were no between-group differences in the short versus standard-length stem groups in terms of mean modified Harris hip score by 5 years after surgery (89 ± 13 versus 95 ± 7 points; p = 0.06). No implant was loose and no hip underwent revision in either group. Patients in the short-stem group showed a slightly smaller decrease in bone mineral density in Gruen Zones 2, 3, and 5 than those in the standard-stem group did; the magnitude of the difference seems unlikely to be clinically important., Conclusion: We found no clinically important differences (and few differences overall) between short and standard-length THA stems 5 years after surgery in a randomized trial. Consequently, we recommend that clinicians use standard-length stems in general practice because standard-length stems have a much longer published track record in other studies, and short stems can expose patients to the uncertainty associated with novelty, without any apparent offsetting benefit., Level of Evidence: Level I, therapeutic study., Competing Interests: All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2020 by the Association of Bone and Joint Surgeons.)

Background: Dissociation between a prosthetic cup and femoral head is a rare complication of bipolar hemiarthroplasty that usually occurs during closed reduction of a dislocated bipolar cup. The dissociation usually results in reoperation because closed reduction is challenging. To our knowledge, no study has reported on the frequency of bipolar cup-femoral head dissociation, and risk factors for dissociation are unknown., Questions/purposes: The purposes of this study were (1) to evaluate the frequency of dissociation of prosthetic femoral heads from bipolar cups during manual reduction of a dislocated bipolar hemiarthroplasty; and (2) to explore in a preliminary fashion any prosthesis or patient factors that may be associated with dissociation., Methods: From May 2003 to August 2016, 60 bipolar hemiarthroplasties were treated at three institutions as a result of early (within 3 years) dislocation after arthroplasty; of these, 55 could be identified and categorized in terms of the type of locking mechanism used, and these were the patients evaluated in this retrospective study. Because the index hemiarthroplasties were not performed exclusively at the three participating centers, we cannot comment on the indications for prosthesis selection in these patients (such as why some patients may have received components with single rather than double locking mechanisms). Manual reduction was attempted in all patients. Although 34 dislocations were manually reduced, 21 hips underwent surgical intervention because they could not be closed reduced (14 hips) or because of bipolar cup-femoral head dissociation (seven hips). We compared patients' demographics and prosthetic factors between the dissociation group (n = 7) and the nondissociation group (n = 48)., Results: Bipolar cup-femoral head dissociation occurred in seven of 55 patients with dislocations (13%). Among the seven dissociated cups, six had a single polyethylene locking ring, whereas 20 of 48 nondissociation cups (42%) had the single locking ring (p = 0.044). We found no other patient or prosthesis factors associated with dissociation., Conclusions: Bipolar cups with a single locking mechanism (rather than a double locking mechanism) may be associated with an increased risk of bipolar cup-femoral head dissociation. However, because we could not evaluate prosthesis indications in this study, and because our sample size was too small to control for potential confounding variables, future studies are needed to confirm this finding. All the same, because good alternatives are available, we do not recommend the use of this type of locking mechanism in bipolar hemiarthroplasty., Level of Evidence: Level III, therapeutic study.

Background: Osteonecrosis of the femoral head frequently leads to collapse of the necrotic portion and subsequent degenerative joint disease of the hip, which is the most common diagnosis leading to total hip arthroplasty in young adults. Bisphosphonate therapy has been reported to potentially retard the collapse. We conducted a two-year prospective, randomized, open-label, multicenter study to determine whether zoledronate prevents the collapse and reduces the need for total hip arthroplasty., Methods: We randomly assigned patients who had Steinberg stage-I or II nontraumatic osteonecrosis of the femoral head with a necrotic area of ≥30% to either the zoledronate group or the control group. Patients in the zoledronate group received 5 mg of zoledronate intravenously per year for two years, while patients in the control group did not receive this medication. The primary efficacy outcome was the survival rate in terms of the occurrence of collapse (≥2 mm). The patients were observed for a minimum of two years after enrollment., Results: A total of 110 patients (110 hips) underwent randomization; fifty-five patients were assigned to the zoledronate group and fifty-five, to the control group. During the two-year follow-up, twenty-nine femoral heads in the zoledronate group and twenty-two in the control group collapsed (p > 0.05). Nineteen hips in the zoledronate group and twenty in the control group underwent total hip arthroplasty (p > 0.05)., Conclusions: Zoledronate for Steinberg stage-I or II osteonecrosis of the femoral head, with a medium to large necrotic area, did not prevent the collapse of the femoral head or reduce the need for total hip arthroplasty., Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence., (Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.)

Diapause-regulated proteins were identified in the CNS of pharate 1st instar larvae of the gypsy moth, Lymantria dispar. Expression of two proteins (130kDa and 45kDa) declined at the time of diapause initiation and remained low during diapause. At diapause termination, following exposure to 5 degrees C for at least 60 days, the 45-kDa protein was again highly expressed. Treatment of young pharate larvae with KK-42 averted diapause, and in such larvae, continued synthesis of the 45 kDa protein in the CNS was observed. These results suggest that expression of the 45-kDa protein is strongly down-regulated in the central nervous system (CNS) during diapause. Partial amino acid sequence determination suggested that the 45-kDa protein is actin, and this was confirmed using anti-actin antibodies. RT-PCR using primers designed from the sequence of the gypsy moth midgut actin mRNA indicated that appearance of actin mRNA in the CNS followed the same pattern as that of the 45-kDa protein. The results indicate that diapause controls actin gene expression in the gypsy moth CNS and regulation is at the transcriptional level.

A nondiapause strain of the gypsy moth offers an additional tool for evaluating the regulation of diapause in this species. Patterns of protein expression in the gut and gut enzyme activity distinguished the two strains. Synthesis of a 55kDa gut protein, previously linked to diapause, began 14days after oviposition in both the diapause (D) and nondiapause (ND) strains. Though synthesis of this protein persisted in the D strain, its synthesis decreased after day 18 in the ND strain. In the D strain, activity of the proteolytic enzymes (trypsin, chymotrypsin, elastase, aminopeptidase) and esterase remained low, while activity of all of these enzymes increased dramatically in the ND strain 18-20days after oviposition. By contrast, alkaline phosphatase (ALP) activity was high in both strains 15-17days after oviposition, activity remained high in the D strain but in the ND strain activity then decreased. Patterns of ALP zymograms were similar in the two strains on day 15, but later a band of high mobility appeared only in the D strain. When 20-hydroxyecdysone was added to hanging drop cultures containing ND pharate larvae 15days after oviposition, the larvae assumed the characteristics of diapause larvae: the 55kDa gut protein was synthesized, the ALP zymogram revealed the characteristic diapause pattern, and they failed to ingest culture medium. The fact that 20-hydroxyecdysone could elicit these responses in ND individuals further supports previous results indicating that ecdysteroids promote the induction and maintenance of the pharate larval diapause in this species.

Several lines of evidence suggest a novel regulatory mechanism for diapause regulation in the gypsy moth. We propose that ecdysteroids play a role in the induction and maintenance of the pharate first instar larval diapause in this species. A 55 kDa gut protein that is indicative of diapause is expressed in intact and neck-ligated pharate larvae but is not expressed when a ligature is placed posterior to the prothorax, site of the prothoracic gland. Guts cultured in vitro for 12 h cease to synthesize the 55 kDa protein, but synthesis of the protein resumes if the culture medium is enriched with a prothorax extract from pharate larvae or a prothoracic gland extract from fifth instar larvae. Injection of 20-hydroxyecdysone or the ecdysteroid agonist, RH-5992, into isolated abdomens stimulates synthesis of the diapause-specific 55 kDa protein, suggesting that the essential factor from the prothorax is an ecdysteroid. KK-42, an imidazole derivative known to inhibit ecdysteroid biosynthesis, averts diapause when applied to prediapausing pharate first instar larvae, but this effect can be countered by application of 20-hydroxyecdysone or RH-5992, i.e. KK-42 treated pharate larvae that are exposed to an ecdysteroid or RH-5992 readily enter diapause. A chilling period (120 days at 5 degrees C) is normally adequate to prompt an immediate termination of diapause when pharate larvae are transferred to 25 degrees C, but if such larvae are held in hanging drop cultures with ecdysteroids they fail to terminate diapause. Together, these results suggest that ecdysteroids are essential for the induction and maintenance of diapause and imply that a drop in the ecdysteroid titer is essential for diapause termination. Copyright 1997 Elsevier Science Ltd. All rights reserved