Phase transitions and optical properties of the semiconducting and metallic phases of single-layer MoS2.

We report density functional theory calculations for single layer MoS2 in its 2H, semiconducting and 1T metallic phases in order to understand the relative stability of these two phases and transition between them in the presence of adsorbed lithium atoms and under compressive strain. We have determined the diffusion barriers between the two phases and demonstrate how the presence of Li adatoms or strain can significantly reduce these barriers. We show that the 2H and 1T structures have the same energy under 15% biaxial, compressive strain. This is the same strain value posited by Lin et al (2014 Nat. Nanotechnology 9 391-396) for their intermediate α phase. Calculations of the 1T and 2H permittivity and electron energy loss spectrum are also performed and characterized.

An evaluation of assumptions underlying respondent-driven sampling and the social contexts of sexual and gender minority youth participating in HIV clinical trials in the United States.

INTRODUCTION: Respondent-driven sampling has been an effective sampling strategy for HIV research in many settings, but has had limited success among some youth in the United States. We evaluated a modified RDS approach for sampling Black and Latinx sexual and gender minority youth (BLSGMY) and evaluates how lived experiences and social contexts of BLSGMY youth may impact traditional RDS assumptions. METHODS: RDS was implemented in three cities to engage BLSGMY in HIV prevention or care intervention trials. RDS was modified to include targeted seed recruitment from venues, internet, and health clinics, and provided options for electronic or paper coupons. Qualitative interviews were conducted among a sub-sample of RDS participants to explore their experiences with RDS. Interviews were coded using RDS assumptions as an analytic framework. RESULTS: Between August 2017 and October 2019, 405 participants were enrolled, 1,670 coupons were distributed, with 133 returned, yielding a 0.079 return rate. The maximum recruitment depth was 4 waves among seeds that propagated. Self-reported median network size was 5 (IQR 2-10) and reduced to 3 (IQR 1-5) when asked how many peers were seen in the past 30 days. Qualitative interviews (n=27) revealed that small social networks, peer trust, and targeted referral of peers with certain characteristics challenged network, random recruitment, and reciprocity assumptions of RDS. HIV stigma and research hesitancy were barriers to participation and peer referral. CONCLUSIONS: Small social networks and varying relationships with peers among BLSGMY challenge assumptions that underlie traditional RDS. Modified RDS approaches, including those that incorporate social media, may support recruitment for community-based research but may challenge assumptions of reciprocal relationships. Research hesitancy and situational barriers must be addressed in recruitment and study designs.

Protein interactions of the MLL PHD fingers modulate MLL target gene regulation in human cells.

The PHD fingers of the human MLL and Drosophila trx proteins have strong amino acid sequence conservation but their function is unknown. We have determined that these fingers mediate homodimerization and binding of MLL to Cyp33, a nuclear cyclophilin. These two proteins interact in vitro and in vivo in mammalian cells and colocalize at specific nuclear subdomains. Overexpression of the Cyp33 protein in leukemia cells results in altered expression of HOX genes that are targets for regulation by MLL. These alterations are suppressed by cyclosporine and are not observed in cell lines that express a mutant MLL protein without PHD fingers. These results suggest that binding of Cyp33 to MLL modulates its effects on the expression of target genes.

Allelic loss and the progression of breast cancer.

To study genetic changes and the evolution of breast cancer, we assayed for loss of heterozygosity (LOH) in 12 sets of synchronous carcinoma in situ (CIS) and invasive cancer, compared to normal control DNA. Microsatellite markers were used, which map to each nonacrocentric autosomal arm. Eight tumor sets demonstrated LOH of the same allele in both concurrent invasive cancer and ductal CIS, for a total of 18 chromosomal loci. Three of nine tumor sets showed LOH on 11p. In two of these sets, LOH was seen on 11p only in the invasive tumor, not the corresponding CIS. One of these tumors also exhibited allelic loss in the invasive tumor for 4 loci, all of which were retained in the noninvasive tumor. For two tumor sets, LOH was mirrored in matched ductal CIS, invasive tumor, and lymph node metastasis. The maintenance of LOH for certain loci throughout the stages of breast cancer suggests clonality of the cancer cells.

Allelic loss on a chromosome 17 in ductal carcinoma in situ of the breast.

Multiple tumor suppressor genes are implicated in the oncogenesis and progression of invasive carcinoma of the breast. To investigate the chronology of genetic changes we studied loss of heterozygosity on chromosome 17 in ductal carcinoma in situ, a preinvasive breast cancer. A microdissection technique was used to separate tumor from normal stromal cells prior to DNA extraction and loss of heterozygosity was assayed mainly using simple sequence repeat polymorphism markers and the polymerase chain reaction. Loss of heterozygosity on 17p was observed in 8 of 28 tumors (29%) when compared with normal control DNA, whereas no loss was seen on 17q, suggesting that at least one locus on 17p is involved early in the development of breast cancer.

Allelic deletion on chromosome 17p13.3 in early ovarian cancer.

Multiple chromosome 17 loci may be involved in ovarian carcinogenesis. Fifty-seven sporadic ovarian epithelial tumors were examined for loss of heterozygosity at 15 loci on chromosomes 17p. Eighty % (39 of 49) of informative tumors had allelic loss in 17p13.3 at D17S30, D17S28, or both loci within this region, including 3 of 7 tumors of low malignant potential and 4 of 5 nonmetastatic carcinomas. The smallest region of overlapping deletions extends from D17S28 to D17S30, a distance of 15 kb. Furthermore, several tumors have breakpoints within the region detected by the D17S30 probe. Chromosome 17p13.3 genes with potential tumor suppressor function include HIC-1, DPH2L (N. J. Phillips et al. Isolation of a human diphthamide biosynthesis gene on chromosome 17p13.3, submitted for publication)/OVCA1, PEDF, and CRK. The HIC-1 coding sequence lies i kb centromeric to the D17S28-S17S30 region of deletion (M. Makos Wales et al., Nat. Med., 1:570-577, 1995) but remains a candidate because 5'-regulatory elements may lie within the critical region. Portions of the DPH2L/OVCA1 coding sequence lie within the D17S28-D17S30 interval. Somatic cell hybrid analysis places PEDF in an interval including D17S28, D17S30, and D17S54, whereas CRK is excluded from this interval. Chromosome 17p13.3 loss precedes TP53 and BRCA1 region deletions because the latter changes are see only in high-stage carcinomas. Microsatellite instability plays only a minor role in sporadic ovarian carcinogenesis because only 1 of 57 tumors showed this finding.

Allelotyping of ductal carcinoma in situ of the breast: deletion of loci on 8p, 13q, 16q, 17p and 17q.

In order to determine which tumor suppressor loci are involved in preinvasive breast cancer, we have assayed for loss of heterozygosity (LOH) in ductal carcinoma in situ (DCIS). Areas of DCIS were microdissected from archival paraffin-embedded tissue. DNA was extracted, and LOH was determined by PCR of microsatellite markers that map to 39 autosomal arms. Either uninvolved lymph node or white cell DNA was used as normal control. A total of 61 samples of DCIS were assayed. The average number of informative tumors examined for each marker was 19 (range, 8-48). The median fractional allelic loss was 0.037. The highest percentage of LOH was shown for loci on 8p (18.7%), 13q (18%), 16q (28.6%), 17p (37.5%), and 17q (15.9%). LOH on 18q was found in 10.7% of informative tumors. Fractional allelic loss was associated with LOH on 17p, with high nuclear grade and with the comedo subtype of DCIS. LOH on 17p correlated with LOH on 17q and on 13q. Additional markers were used for 16q and 17p to determine the smallest common region of deletion. These data provide evidence that tumor suppressor loci that map to these regions are involved in the oncogenesis of breast cancer before progression to the invasive phenotype. Our findings provide additional support that multiple loci on 17p and 16q are involved in the development of breast cancer.

Determination of the elastic properties of graphene by indentation and the validity of classical models of indentation.

Ab initio and empirical force field methods are used to simulate the loading of a large graphene membrane under an indenter analogous to an atomic force microscope tip. From these calculations we attempt to resolve ambiguities around determination of the elastic constants of graphene from such indentation experiments. We investigate the effect of the formation of wrinkles and more importantly the applicability of modelling the membrane as a continuous elastic sheet. By comparing empirical potential and large scale density functional theory calculations we have also assessed the performance of classical potentials in describing bending in this system. We find that the in-plane Young's modulus deduced from the indentation simulations using the classical expression for a clamped elastic membrane under a central point load is not consistent with that calculated directly from the in-plane stress-strain curve.

Comparative utility of diagnostic bone-marrow components: a 10-year study.

Ten years of cumulative experience represented by 4,902 consecutive diagnostic bone-marrow examinations at a tertiary care and referral center were reviewed to assess the value of specific components. While it has been shown previously that the information obtained from each component is generally complementary, the inclusion of some or all components may vary between institutions. The components studied included aspirate smears, clot sections, biopsy cores, and touch imprints of biopsy and clot sections. Three clinical presentations accounted for the majority of cases: staging for carcinoma or lymphoma, cytopenias, and acute leukemia. We conclude that bilateral aspirates with biopsies are required for diagnosis in staging of neoplasms and that a unilateral aspirate with biopsy is sufficient to assess patients with cytopenia or leukemia. Only rarely were touch imprints of biopsy cores necessary to establish a diagnosis; however, their early availability prior to examining sections of the clot and core did provide immediate information, when positive, in the staging of patients with carcinoma. In a small percentage of staging and leukemia cases the diagnosis rested with the clot section alone. The findings in this study address common assumptions associated with routine diagnostic hematology and oncology procedures, and are important to both clinicians and pathologists concerned with accuracy, quality assurance, turnaround time, and cost containment.

Aortic angiosarcoma presenting with cutaneous metastasis: case report and review of the literature.

Aortic angiosarcoma is a rare malignancy. Clinical diagnosis is difficult, as the presenting symptoms mimic more common aortic lesions, particularly atherosclerosis. Dermatologists and dermatopathologists play a critical role in recognizing cutaneous metastases as a manifestation of this life-threatening tumor. We describe the fourth case of aortic angiosarcoma in the literature with initial presentation in the skin.

Cutaneous deciduosis.

Cutaneous deciduosis is an exceedingly rare manifestation of endometriosis potentially mistaken for malignancy and thus far documented solely within surgical scars. We describe two additional cases, one occurring in a pregnant 21-year-old woman as a solitary flat erythematous vulvar papule, an extraordinary location not previously recorded. Histologic examination in that case revealed a subepithelial nodular aggregate of atypical large dyscohesive cells with accompanying edema and inflammation. An immunohistochemical panel showed positivity of the cells for vimentin and Ki-1 (CD30). Intracellular sulfated mucin and glycogen were also demonstrated. In a second case, a 27-year-old woman had a nodule at the umbilicus, removed incidentally during the course of cesarean section. Microscopically there were several circumscribed, multilobulated, intradermal nodules with variably sized lumens formed by crowded large epithelioid cells. The disparate histologic appearance of these examples highlights an essential challenge in their diagnosis. Clinical recognition is difficult unless suggested by more characteristic history or location.

A comparison of melanin bleaching and azure blue counterstaining in the immunohistochemical diagnosis of malignant melanoma.

Distinguishing heavily pigmented melanocytes from melanophages on routine hematoxylin and eosin slides can be difficult. Melanin bleaching with potassium permanganate solution is a traditional means of removing melanin from tissues and can be used before immunohistochemical staining to remove any pigment that might be confused with the brown chromogen diaminobenzidine. Azure B stains melanin granules green-blue, easily contrasts with diaminobenzidine, and may be used as a counterstain on unbleached sections after immunohistochemical staining. To our knowledge, studies comparing melanin bleaching with azure B counterstaining in the immunohistochemical evaluation of malignant melanomas have not been performed. Paraffin sections from 33 heavily pigmented malignant melanomas were bleached with a 3.0-g/L potassium permanganate solution, immunohistochemically stained for S-100 and HMB-45, and counterstained with hematoxylin. Unbleached sections were similarly stained for S-100 and HMB-45 and counterstained with azure B. To establish optimal permanganate concentrations, a variable number of sections were bleached with lower permanganate concentrations ranging from 0.125 to 2.5 g/L. S-100 antigenicity was preserved at all permanganate concentrations, whereas HMB-45 antigenicity was abolished at concentrations of 0.5 g/L and greater. At permanganate concentrations from 0.125 to 0.5 g/L, both antigenicities were preserved; however, melanin was incompletely removed. Complications of bleaching included tissue damage and loss of cytologic detail. Positive immunohistochemical staining was observed in azure B counterstained sections. Azure B stained melanin greenblue and was easily distinguished from the brown diaminobenzidine chromogen, regardless of the antibody tested. Neither tissue damage nor loss of cytologic detail was observed. We conclude that the use of azure B counterstaining is superior to permanganate bleaching in the histologic evaluation of heavily pigmented cutaneous malignant melanomas.

Squamous cell carcinoma arising in Hailey-Hailey disease.

Hailey-Hailey disease is a recurrent, autosomal dominant vesiculobullous dermatotis with a predilection for intertrigenous areas. We report what we believe to be the first case of squamous cell carcinoma arising de novo in a skin lesion of Hailey-Hailey disease. The occurrence of malignant neoplasms arising in the skin lesions of Hailey-Hailey disease and other acantholytic dermatoses is reviewed.

Lipedematous alopecia: a clinicopathologic, histologic and ultrastructural study.

Lipedematous alopecia is a rare condition of unknown etiology characterized by a thick, boggy scalp with varying degrees of hair loss that occurs in adult black females, with no clearly associated medical or physiologic conditions. The fundamental pathologic finding consists of an approximate doubling in scalp thickness resulting from expansion of the subcutaneous fat layer in the absence of adipose tissue hypertrophy or hyperplasia. Observations by light and electron microscopy detailed in this report suggest that this alteration principally manifests by localized edema with disruption and degeneration of adipose tissue. Some diminution in the number of follicles as well as focal bulb atrophy is noted. Aberrant mucin deposition such as that seen in myxedema or other cutaneous mucinoses is not a feature. The histologic findings bear some resemblance to those seen in lipedema of the legs, a relatively common but infrequently diagnosed condition. We present a case of lipedematous alopecia with emphasis on histologic and ultrastructural features. The etiology is unknown.

Sequence-ready contig for the 1.4-cM ductal carcinoma in situ loss of heterozygosity region on chromosome 8p22-p23.

We report the construction of an approximately 1.7-Mb sequence-ready YAC/BAC clone contig of 8p22-p23. This chromosomal region has been associated with frequent loss of heterozygosity (LOH) in breast, ovarian, prostate, head and neck, and liver cancer. We first constructed a meiotic linkage map for 8p to resolve previously reported conflicting map orders from the literature. The target region containing a putative tumor suppressor gene was defined by allelotyping 65 cases of sporadic ductal carcinoma in situ with 18 polymorphic markers from 8p. The minimal region of loss encompassed the interval between D8S520 and D8S261, and one tumor had loss of D8S550 only. We chose to begin physical mapping of this minimal LOH region by concentrating on the distal end, which includes D8S550. A fine-structure radiation hybrid map for the region that extends from D8S520 (distal) to D8S1759 (proximal) was prepared, followed by construction of a single, integrated YAC/BAC contig for the interval. The approximately 1730-kb contig consists of 13 YACs and 27 BACs. Fifty-four sequence-tagged sites (STSs) developed from BAC insert end-sequences and 11 expressed sequence tags were localized within the contig by STS content mapping. In addition, four unique cDNA clones from the region were isolated and fully sequenced. This integrated YAC/BAC resource provides the starting point for transcription mapping, genomic sequencing, and positional cloning of this region.