Ab initio study of temperature-dependent piezoelectric and electronic properties of thermally stable GaPO4.

Gallium-phosphate (GaPO4) is one of the ultra-high thermally stable piezoelectric materials with a high critical temperature of 1206 K. Here, first principles calculations with quasi-harmonic approximation are performed to study thermal and other physical properties of α-GaPO4. For the electronic structure, we focus on the electron-phonon interaction and lattice expansion effects on the temperature-dependent band gap, which plays a significant role in zero-point renormalization. Significantly, the large piezoelectric constants e11 primarily comes from intrinsic sensitivity of Ga and O sites to axial strain, while P atoms contribute little, which remains true in other quartz-like type APO4 (A = B, Al, In). Our work provides an insight into the temperature-dependent electronic and piezoelectric properties of α-GaPO4 and motivates its applications in a high temperature environment.

The impact of surgical downgrading on prostate cancer recurrence: systematic review and analysis of a multiethnic population.

OBJECTIVE: To perform a systematic review and a retrospective cohort analysis evaluating the rates of surgical downgrading of prostate cancer (PCa) from biopsy (PBx) to radical prostatectomy (RP), and their association with biochemical recurrence (BCR) in a multiethnic population. METHODS: A systematic review of PubMed and other databases was performed. We included retrospective studies evaluating the relationship between surgical downgrading and BCR-free survival. Data regarding Gleason score (GL) downgrading were abstracted from the articles and categorized as follows: GL8-10 to GL7, GL7 to GL6, and GL 7(4 + 3) to GL7(3 + 4). We also performed a retrospective cohort review of patients who underwent RP at our institution from 2005 through 2020. Kaplan-Meier survival analysis and Cox proportional hazards models were used to compare BCR among downgraded versus non-downgraded men. RESULTS: Systematic review yielded 137 abstracts; of these, 36 full-texts were reviewed, 8 of which were included in our systematic review. Despite substantial variability, all showed that GL at RP is one of the most important factors of BCR-free survival. A total of 1,484 men with PCa were analyzed from our institution. On multivariate analysis, GL7 to GL6 downgrading (HR = 0.50, p = 0.022) and GL8-10 to GL7 downgrading (HR = 0.42, p = 0.011) were associated with reduced risk of BCR when compared to men with GL7 and GL8-10 concordance, respectively. However, GL7(4 + 3) to GL7(3 + 4) downgrading was not significantly associated with reduced BCR (HR = 0.56, p = 0.12), when compared to GL7(4 + 3) concordance, although HR was similar. CONCLUSION: Surgical downgrading at RP was associated with a reduced risk of BCR compared to GL concordant disease, and these findings have been validated within our multiethnic population. Pathologic downgrading at the time of RP may be a more useful predictor of subsequent BCR in comparison to that associated with GL concordant pathology.

Clinical challenges of scrotal lymphangioma in an adult: a rare case of scrotal swelling.

Scrotal lymphangiomas represent an extremely rare cause of scrotal swelling. We report a case of scrotal lymphangioma in an 18-year-old male who presented with painful scrotal swelling. Scrotal ultrasound revealed a complex multicystic structure in the left hemiscrotum. The patient underwent successful surgical excision of the mass. Postoperatively, he developed a hydrocele which eventually spontaneously regressed. Histopathology confirmed the diagnosis. We outline the unusual presentation, characteristic imaging and histology findings, and surgical management of scrotal lymphangiomas. With this information, urologists may exercise a heightened level of awareness for this rare cause of scrotal swelling.

Predicting the structural, electronic and magnetic properties of few atomic-layer polar perovskite.

Density functional theory (DFT) calculations are performed to predict the structural, electronic and magnetic properties of electrically neutral or charged few-atomic-layer (AL) oxides based on polar perovskite KTaO3. Their properties vary greatly with the number of ALs (nAL) and the stoichiometric ratio. In the few-AL limit (nAL ≤ 14), the even AL (EL) systems with the chemical formula (KTaO3)n are semiconductors, while the odd AL (OL) systems with the formula Kn+1TanO3n+1 or KnTan+1O3n+2 are half-metal except for the unique KTa2O5 case which is a semiconductor due to the large Peierls distortions. After reaching a certain critical thickness (nAL > 14), the EL systems show ferromagnetic surface states, while ferromagnetism disappears in the OL systems. These predictions from fundamental complexity of polar perovskite when approaching the two-dimensional (2D) limit may be helpful for interpreting experimental observations later.

Impact of devascularization and tissue procurement on cell number and RNA integrity in prostatectomy tissue.

BACKGROUND: Minimizing the time between tissue devascularization in robot-assisted laparoscopic radical prostatectomy (RALP) and tissue procurement should produce the highest quality tissue for research study. This study examines the relationship between intra-operative time and two indicators of tissue integrity: number of epithelial cells per gram of tissue and RNA integrity numbers (RINs). The study also compares the RIN values of tissue obtained intra-operatively by biopsy, before and after devascularization, to those from RALP specimen tissue, obtained through the routine research tissue procurement process. METHODS: Prostate tissues from two series of patients were analyzed. In the first, tissue from 18 patients undergoing RALP was analyzed for number of epithelial cells per gram of tissue. In the second, RIN values of tissue from 46 patients involved in a clinical study were analyzed. RIN values were assessed from RALP specimen tissue as well as tissue removed intra-operatively by biopsy, before and after devascularization. RESULTS: Time from RALP to tissue procurement was not significantly associated with number of epithelial cells per gram of tissue or with RIN values. RINs of biopsy tissue obtained intra-operatively before and after devascularization were similar. However, the RIN values of tissue from RALP specimens were significantly higher than those of biopsy tissue obtained either before or after devascularization. CONCLUSIONS: Tissue quality, defined by number of epithelial cells or RIN values, was not affected by time between devascularization and procurement. Obtaining tissue from intra-operative biopsies, either before or after devascularization, is not necessary and actually produced lower RINs than found in tissue from RALP specimens, obtained through the routine research tissue procurement process.

Case report: Isolated oligometastatic disease of the prostate from a primary lung adenocarcinoma.

Secondary prostate cancer typically occurs from direct seeding of a renal or bladder tumor. Metastasis via hematogenous spread is exceedingly rare and is typically identified incidentally at autopsy. This report describes a 72-year-old male with lung adenocarcinoma initially staged as Stage IA2 who developed oligometastatic disease of the prostate. He was initially treated with radiation therapy and was found to have a hypermetabolic focus in the prostate gland during surveillance PET/CT imaging 6 months following treatment. Subsequent biopsy revealed metastatic lung adenocarcinoma in 6/6 core samples, leading to diagnosis of oligometastatic disease of the prostate. To our knowledge, this is the first report of isolated oligometastatic disease to the prostate from a primary lung adenocarcinoma.

The direct inhibitory effect of dutasteride or finasteride on androgen receptor activity is cell line specific.

BACKGROUND: Finasteride and dutasteride were developed originally as 5α-reductase inhibitors to block the conversion of testosterone to dihydrotestosterone (DHT). These drugs may possess off-target effects on the androgen receptor (AR) due to their structural similarity to DHT. METHODS: A total of four human prostate cancer cell models were examined: LNCaP (T877A mutant AR), 22Rv1 (H874Y mutant AR), LAPC4 (wild-type AR), and VCaP (wild-type AR). Cells were cultured in 10% charcoal-stripped fetal bovine serum, either with or without DHT added to the medium. AR activity was evaluated using the ARE-luciferase assay or the expression of AR regulated genes. RESULTS: Dutasteride was more potent than finasteride in interfering with DHT-stimulated AR signaling. Disruption of AR function was accompanied by decreased cell growth. Cells that rely on DHT for protection against death were particularly vulnerable to dutasteride. Different prostate cancer cell models exhibited different sensitivities to dutasteride and finasteride. LNCaP was most sensitive, LAPC4 and VCaP were intermediate, while 22Rv1 was least sensitive. Regardless of the AR genotype, if AR was transfected into drug-sensitive cells, AR was inhibited by drug treatment; and if AR was transfected into drug-resistant cells, AR was not inhibited. CONCLUSIONS: The direct inhibitory effect of dutasteride or finasteride on AR signaling is cell line specific. Mutations in the ligand binding domain of AR do not appear to play a significant role in influencing the AR antagonistic effect of these drugs. Subcellular constituent is an important factor in determining the drug effect on AR function.

Diagnosis and Treatment of a Mixed Epithelial Stromal Tumor of the Seminal Vesicle: A Systematic Review.

OBJECTIVE: To perform a systematic review of mixed epithelial stromal tumor of the seminal vesicle (SV) to characterize the diagnosis and treatment of this rare condition. METHODS: "Seminal vesicle mixed epithelial stromal tumor" OR "seminal vesicle cystadenoma" were searched on PubMed/MEDLINE for relevant articles through 6 September 2021. Articles were eligible if they were in English, accessible via our university library services, and if the abstract was concordant with the content of the publication. Reference lists of included articles were reviewed to identify additional relevant articles. RESULTS: In total, 66 articles were identified, of which 34 (N = 36 patients) were included. The most common presenting symptoms were lower urinary tract symptoms (33%, 12/36), dysuria (22%, 8/36), lower abdominal pain (17%, 6/36), and hematuria (17%, 6/36). However, there were eight cases (23%, 8/36) of asymptomatic incidental SV tumors. A biopsy was performed in 47% of cases (17/36), of which 53% (9/17) showed benign findings, 29% (5/17) were inconclusive, and 18% (3/17) SV cystadenoma. Surgical resection was performed using open (57%, 20/35), laparoscopic (26%, 9/35), or robotic (17%, 6/35) techniques. The majority (94%, 34/36) of the SV tumors were low-grade. Long-term follow-up was reported for 15 patients in which two patients (13%, 2/15) had tumor recurrence. CONCLUSION: High rate of inconclusive biopsy of SV tumors suggests that routine biopsy is of questionable utility. Surgical excision frequently relieves symptoms and confirms accurate pathologic diagnosis. After tumor removal, patients should be surveilled with cross-sectional imaging of the pelvis given the possibility of tumor recurrence.

Ureteral metastasis in colorectal cancer: A case report and review of literature.

Colorectal cancer (CRC) is a common clinical entity. A significant proportion of patients experience metastatic disease, typically in the form of lung and liver spread. We present the case of a CRC cancer patient with distant metastasis to the ureter, causing hydronephrosis. Ureteroscopy and biopsy confirmed the diagnosis and the patient was subsequently treated with percutaneous nephrostomy tube placement. Distant spread of CRC to the ureter represents an exceedingly rare phenomenon. This case highlights the importance of heightened index of suspicion for ureteral involvement in CRC when hydronephrosis is identified on staging or surveillance cross sectional imaging.

High Weight-Specific Power Density of Thin-Film Amorphous Silicon Solar Cells on Graphene Papers.

Flexible thin-film solar cells with high weight-specific power density are highly desired in the emerging portable/wearable electronic devices, solar-powered vehicles, etc. The conventional flexible metallic or plastic substrates are encountered either overweight or thermal and mechanical mismatch with deposited films. In this work, we proposed a novel substrate for flexible solar cells based on graphene paper, which possesses the advantages of being lightweight and having a high-temperature tolerance and high mechanical flexibility. Thin-film amorphous silicon (a-Si:H) solar cells were constructed on such graphene paper, whose power density is 4.5 times higher than that on plastic polyimide substrates. In addition, the a-Si:H solar cells present notable flexibility whose power conversion efficiencies show little degradation when the solar cells are bent to a radius as small as 14 mm for more than 100 times. The application of this unique flexible substrate can be extended to CuInGaSe and CdTe solar cells and other thin-film devices requiring high-temperature processing.

Improvement in dielectric and tunable properties of Fe-doped Ba0.6Sr0.4TiO3 thin films grown by pulsed-laser deposition.

Fe-doped Ba(0.6)Sr(0.4)TiO3 (BST) thin films were prepared on Pt/Si substrates by the pulsed-laser deposition method. The concentrations of Fe dopants vary from 0.1 mol% to 1.0 mol%. Our results indicate that a certain amount of Fe dopants can decrease the dielectric loss of BST thin films without causing the significant reduction of the tunability. The leakage current of BST thin films also was reduced by the addition of Fe dopants. BST thin films doped with 0.3 mol% Fe ions show a minimum dielectric loss of 0.88% at 10(6) Hz, which is 1.7% for the undoped BST films. Moreover, the 0.3 mol% Fe-doped BST films reveal a maximum figure of merit (FOM) of 51, indicating the improved comprehensive dielectric and tunable properties.

Effects of La concentration on the structural and dielectric properties of 0.57BiFeO3-0.43PbTiO3 crystalline solutions.

Crystalline solutions of 0.57(Bi(1-x)La(x))FeO(3)-0.43PbTiO(3) (BLF-PT) for x = 0, 0.1, 0.2, and 0.3 were fabricated by the traditional solid state reaction method. X-ray diffraction analysis revealed that the tetragonal torhombohedral phase transformation of BLF-PT occurred with an increase of the La content. The dielectric and ferroelectric properties of BLF-PT were investigated at room temperature for different La contents. BLF-PT revealed strong ferroelectric characteristics for the lower La composition, and transferred to relaxor ferroelectrics for x 0.2. The dielectric constant and remanent polarization were 1461 and 33.5 microC/cm(2), respectively, for BLF-PT of x = 0.2. The dielectric constant and polarization of BLF-PT were enhanced simultaneously with increasing La content. Our results demonstrate that BLF-PT is a competitive piezoelectric ceramic.

Multiple mechanisms underlie resistance of leukemia cells to Apo2 Ligand/TRAIL.

Targeting death receptors with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has the remarkable potential to selectively kill malignant cells whereas normal cells are largely unaffected by this treatment. However, some tumor cells, including leukemia cells, exhibit resistance to this molecule. To investigate the basis for resistance of leukemia cells to the zinc-bound form of Apo2 ligand (Apo2L)/TRAIL, which is currently being evaluated in clinical trial, we isolated several resistant HL60 clones from parental HL60 cells by selection using the recombinant Apo2L/TRAIL. Differing resistance mechanisms were identified and characterized in these Apo2L/TRAIL-resistant clones. In one case, the level of the cell-surface death receptor DR4, but not DR5, was significantly decreased. However, these cells did undergo apoptosis in response to another form of recombinant TRAIL, histidine-tagged TRAIL, suggesting differing contributions of DR4 and DR5 in the response to these two forms of TRAIL. In the case of other clones, expression of procaspase-8 protein was lost and this was associated with a novel Leu(22)-->Phe(22) point mutation in CASP-8 gene. These results show that cells within a given tumor can have widely distinct mechanisms underlying resistance to Apo2L/TRAIL.

Enhanced Actuation Performance and Reduced Heat Generation in Shear-Bending Mode Actuator at High Temperature.

The actuation performance, strain hysteresis, and heat generation of the shear-bending mode actuators based on soft and hard BiScO3-PbTiO3 (BS-PT) ceramics were investigated under different thermal (from room temperature to 300 °C) and electrical loadings (from 2 to 10 kV/cm and from 1 to 1000 Hz). The actuator based on both soft and hard BS-PT ceramics worked stably at the temperature as high as 300 °C. The maximum working temperature of this shear-bending actuators is 150 °C higher than those of the traditional piezoelectric actuators based on commercial Pb(Zr, Ti)O3 materials. Furthermore, although the piezoelectric properties of soft-type ceramics based on BS-PT ceramics were superior to those of hard ceramics, the maximum displacement of the actuator based on hard ceramics was larger than that fabricated by soft ceramics at high temperature. The maximum displacement of the actuator based on hard ceramics was [Formula: see text] under an applied electric field of 10 kV/cm at 300 °C. The strain hysteresis and heat generation of the actuator based on hard ceramics was smaller than those of the actuator based on soft ceramics in the wide temperature range. These results indicated that the shear-bending actuator based on hard piezoelectric ceramics was more suitable for high-temperature piezoelectric applications.

The anti-tumor effect of Apo2L/TRAIL on patient pancreatic adenocarcinomas grown as xenografts in SCID mice.

BACKGROUND: Apo2L/TRAIL has considerable promise for cancer therapy based on the fact that this member of the tumor necrosis factor family induces apoptosis in the majority of malignant cells, while normal cells are more resistant. Furthermore, in many cells, when Apo2L/TRAIL is combined with chemotherapy, the effect is synergistic. The majority of this work has been carried out using cell lines. Therefore, investigation of how patient tumors respond to Apo2L/TRAIL can validate and/or complement information obtained from cell lines and prove valuable in the design of future clinical trials. METHODS: We have investigated the Apo2L/TRAIL sensitivity of patient derived pancreatic tumors using a patient tumor xenograft/ SCID mouse model. Mice bearing engrafted tumors were treated with Apo2L/TRAIL, gemcitabine or a combination of both therapies. RESULTS: Patient tumors grown as xenografts exhibited a spectrum of sensitivity to Apo2L/TRAIL. Both Apo2L/TRAIL sensitive and resistant pancreatic tumors were found, as well as tumors that showed heterogeneity of response. Changes in apoptotic signaling molecules in a sensitive tumor were analyzed by Western blot following Apo2L/TRAIL treatment; loss of procaspase 8, Bid and procaspase 3 was observed and correlated with inhibition of tumor growth. However, in a tumor that was highly resistant to killing by Apo2L/TRAIL, although there was a partial loss of procaspase 8 and Bid in response to Apo2L/TRAIL treatment, loss of procaspase 3 was negligible. This resistant tumor also expressed a high level of the anti-apoptotic molecule Bcl-XL that, in comparison, was not detected in a sensitive tumor. Importantly, in the majority of these tumors, addition of gemcitabine to Apo2L/TRAIL resulted in a greater anti-tumor effect than either therapy used alone. CONCLUSION: These data suggest that in a clinical setting we will see heterogeneity in the response of patients' tumors to Apo2L/TRAIL, including tumors that are highly sensitive as well as those that are resistant. While much more work is needed to understand the molecular basis for this heterogeneity, it is very encouraging, that Apo2L/TRAIL in combination with gemcitabine increased therapeutic efficacy in almost every case and therefore may be a highly effective strategy for controlling human pancreatic cancer validating and expanding upon what has been reported for cell lines.

The transcriptomics of de novo androgen biosynthesis in prostate cancer cells following androgen reduction.

The progression of prostate cancer to the castration-recurrent phenotype remains a major problem medically. The present study examined the transcriptomics of de novo androgen synthesis as a potential mechanism to escape from dependence on circulating androgen. VCaP, LNCaP and LAPC4 cells were acclimated to 1 nM testosterone for five generations before subjecting them to a reduced level of 0.03 nM testosterone. Changes in gene expression were quantified using qRT-PCR. Analyses of the cholesterol biosynthesis pathway and the Δ4, Δ5 and backdoor steroidogenic pathways were carried out. VCaP cells showed no change in the transcriptome of cholesterol biosynthesis. However, several receptors for cholesterol transport were upregulated. The Δ4 and Δ5 steroidogenic pathways, but not the backdoor pathway, were stimulated. Additionally, androgen receptor (AR) expression was increased. Taken together, the above changes might allow recovery of AR activity to a near normal level. In contrast, LNCaP cells showed only minimal adjustment in the transcriptome of steroidogenesis. LAPC4 cells were equally unresponsive to boosting the machinery of androgen production. In brief, our results suggest that the VCaP model is an appropriate model for further investigation of targeting the androgen-AR axis to block the emergence of castration-resistant prostate cancer.

Androgen receptor-mTOR crosstalk is regulated by testosterone availability: implication for prostate cancer cell survival.

BACKGROUND: Signaling between androgen receptor (AR) and mTOR may be crucial for prostate cancer cells to endure the low androgen and suboptimal nutrient conditions produced by androgen deprivation therapy. MATERIALS AND METHODS: AR and mTOR cross-talk was examined in LNCaP cells exposed to either high or low testosterone. AR and mTOR activities were modified separately using either siRNA knockdown or specific chemical inhibitor. The biological significance of the reciprocal communication was assessed by susceptibility to glucose deprivation-induced cell death. RESULTS: AR positively regulated mTOR activity in both low and high testosterone levels. TSC1 and TSC2, the two negative regulators of mTOR, may be involved since both were up-regulated by AR knockdown. Sub-baseline mTOR increased AR protein levels. However, this effect only occurred with low testosterone. More cells underwent apoptosis if AR function was inhibited during glucose deprivation, which significantly depressed mTOR activity. CONCLUSION: The compensatory increase of AR function due to a repressed mTOR signal is advantageous for survival. Disrupting this loop at the time of initiation of androgen deprivation therapy may delay, or even prevent, the recurrence of prostate cancer.

A high temperature piezoelectric ceramic: (1-x)(Bi0.9La0.1)FeO(3-x)PbTiO3 crystalline solutions.

(1-x)(Bi(0.9)La(0.1))FeO(3-x)PbTiO(3) (BLF-PT) crystalline solutions for x = 0.35, 0.37, 0.4, 0.43 and 0.45 have been prepared by the solid-state reaction method. The X-ray diffraction analysis shows that BLF-PT has a single perovskite phase with mixed tetragonal and rhombohedral phases between x = 0.4 and 0.43. The Curie temperature of BLF-PT for x = 0.4 attains 460 degrees C, which is about 80 degrees C higher than that of hard Pb(Zr,Ti)O(3) ceramics. The remnant polarization and piezoelectric constant of BLF-PT for x = 0.4 reach 38 microC/cm(2) and 112 pC/N, respectively. The planar coupling factor k(p) of BLF-PT for x = 0.4 remains stable at temperature increases of up to 360 degrees C. The impedance spectroscopy study reveals that the high temperature conduction of BLF-PT may be attributed to the motion of oxygen vacancies within the material. Our results indicate that BLF-PT is a promising candidate for high temperature applications.

Effects of gallium on the structure and electrical properties of 0.65 (Bi0.94La0.06) (Ga(x)Fe(1-x))O3-0.35PbTiO3 ceramics.

Crystalline solutions of 0.65 Bi(0.94)La(0.06)) (Ga(x)Fe(1-x))O(3)-0.35PbTiO(3) Ceramics (BLGF-PT) for x = 0 and 0.05 have been fabricated by the solid-state reaction method. X-ray diffraction (XRD) was utilized to characterize the crystal structure and examine any possible impurities existing in the ceramics. The effects of Ga substitution on dielectric properties of the samples were studied at frequencies from 10(2) to 10(6) Hz over a temperature range from 20 to 620 degrees C. The results indicate that Ga modification can reduce the room temperature dielectric loss. The conduction mechanism of the material was investigated using ac conductivity. It is concluded that electrons originating from Fe(2+) and oxygen ion vacancies are the main charge carriers, and Ga doping could decrease the electronic conduction effectively. The frequency dependence of ac conductivity was found to follow Jonscher's universal power law.

Targeting the oncogene and kinome chaperone CDC37.

CDC37 is a molecular chaperone that physically stabilizes the catalytic domains found in protein kinases and is therefore a wide-spectrum regulator of protein phosphorylation. It is also an overexpressed oncoprotein that mediates carcinogenesis by stabilizing the compromised structures of mutant and/or overexpressed oncogenic kinases. Recent work shows that such dependency of malignant cells on increased CDC37 expression is a vulnerability that can be targeted in cancer by agents that deplete or inhibit CDC37. CDC37 is thus a candidate for broad-spectrum molecular cancer therapy.