Using deep learning to detect digitally encoded DNA trigger for Trojan malware in Bio-Cyber attacks.

This article uses Deep Learning technologies to safeguard DNA sequencing against Bio-Cyber attacks. We consider a hybrid attack scenario where the payload is encoded into a DNA sequence to activate a Trojan malware implanted in a software tool used in the sequencing pipeline in order to allow the perpetrators to gain control over the resources used in that pipeline during sequence analysis. The scenario considered in the paper is based on perpetrators submitting synthetically engineered DNA samples that contain digitally encoded IP address and port number of the perpetrator's machine in the DNA. Genetic analysis of the sample's DNA will decode the address that is used by the software Trojan malware to activate and trigger a remote connection. This approach can open up to multiple perpetrators to create connections to hijack the DNA sequencing pipeline. As a way of hiding the data, the perpetrators can avoid detection by encoding the address to maximise similarity with genuine DNAs, which we showed previously. However, in this paper we show how Deep Learning can be used to successfully detect and identify the trigger encoded data, in order to protect a DNA sequencing pipeline from Trojan attacks. The result shows nearly up to 100% accuracy in detection in such a novel Trojan attack scenario even after applying fragmentation encryption and steganography on the encoded trigger data. In addition, feasibility of designing and synthesizing encoded DNA for such Trojan payloads is validated by a wet lab experiment.

Resequencing microarray method for molecular diagnosis of human arboviral diseases.

BACKGROUND: Resequencing DNA microarray (RMA) technology uses probes designed to identify a panel of viral sequences. It can be used for detecting emerging viruses by revealing the nucleotide polymorphisms within the target of interest. OBJECTIVES/STUDY DESIGN: As a new tool for molecular diagnosis of arbovirus infection, high density PathogenID v2.0 RMA (PID2-RMA) was assessed for the detection and genetic analysis of dengue, West Nile, and Chikungunya viruses in spiked blood samples or sera from individuals infected with dengue virus. Viral RNAs extracted from biological samples were retrotranscribed into cDNA and amplified using the Phi 29 polymerase-based method. This amplified cDNA was used for hybridization on PID2-RMA. RESULTS: A good specificity of RMA-based detection was demonstrated using a panel of arboviruses including Dengue, West Nile and Chikungunya viruses. This technology was also efficient for the detection and genetic analysis of the different serotypes of dengue virus in sera of infected patients. Furthermore, the mixing of dengue, West Nile and Chikungunya prototype viruses within a single sample of human blood did not interfere with the sensitivity of PID2-RMA. CONCLUSIONS: Our data show that high density PID2-RMA was suitable for the identification of medically important arboviruses. It appears to be particularly adapted to the genetic analysis of dengue, West Nile, and Chikungunya viruses in urgent clinical situations where the rapid identification and characterization of the pathogen is essential.

Audit on breast ultrasound in women under 25 years.

BACKGROUND: Women younger than 30 years with a focal breast finding have a low incidence of malignancy. Targeted ultrasound is an accurate primary imaging test. MATERIALS AND METHODS: All breast ultrasounds performed from July 1, 2011 to September 30, 2011 were reviewed. All ultrasounds in patients under 25 years were reviewed with regard to indication, imaging findings, and pathology results. RESULTS: Over a 3-month period, 855 breast ultrasounds were performed; 4.1 % breast ultrasounds were performed in a patient under 25 years. Twenty patients had imaging features consistent with a fibroadenoma. Pathology confirmed the diagnosis of fibroadenomas in 15 of the patients. Five patients did not have biopsies performed due to young age or presence of bilateral fibroadenoma. CONCLUSION: A breast nodule in a patient under the age of 25 years with benign clinical findings and imaging features consistent with a fibroadenoma does not require biopsy.

Eliashberg analysis of tunneling experiments: support for the pairing glue hypothesis in cuprate superconductors.

Evidence for the validity of the pairing glue interpretation of high temperature superconductivity is presented using a modified Eliashberg analysis of experimental superconductor-insulator-superconductor (SIS) tunneling data in B2Sr2CaCu2O8 (Bi2212) over a wide range of doping. This is accomplished by extracting detailed information on the diagonal and anomalous contributions to the quasiparticle self-energy. In particular, a comparison of the imaginary part of the anomalous self-energy ImΦ(ω) and the pairing glue spectral function α2F(ω) used in the model is consistent with Hubbard model simulations in the literature. In addition, the real part of the diagonal self-energy for optimal doped Bi2212 bears a strong resemblance to that obtained from photoemission experiments.

The characterization of Listeria spp. isolated from food products and the food-processing environment.

AIM: To enhance the information pertaining to the epidemiology of a collection of 378 Listeria spp. isolates obtained from several food-processing plants in Ireland over a 3-year period (2004-2007). METHODS AND RESULTS: The collection was characterized by pulsed-field gel electrophoresis (PFGE). The most prevalent pulse-type was PFGE profile I (n=14·5%) that consisted mainly of environmental Listeria spp. samples. Serotyping of 145 Listeria monocytogenes isolates was performed. The most common serovar was 1/2a and comprised 57·4% (n=77) of the L. monocytogenes collection. The other serovars were as follows: 4b (14·1%, n=19), 1/2b (9·7%, n=13), 4c (4·4%, n=6) and 1/2c (6·7%, n=9), respectively. Eleven isolates were identified as non-Listeria spp., the remaining ten L. monocytogenes isolates were nontypeable. The antimicrobial susceptibility testing revealed the antibiotic that isolates displayed the most resistance to was gentamicin (5%) followed by sulfamethoxazole-trimethoprim (2%), tetracycline and ciprofloxacin (1·5%). CONCLUSIONS: The subtyping has indicated the diversity of the Listeria spp. The presence of serotype 1/2a, 1/2b and 4b in both raw and cooked ready-to-eat food products is a public health concern, as these serotypes are frequently associated with foodborne outbreaks and sporadic cases of human listeriosis. In addition, the emergence of antimicrobial-resistant L. monocytogenes isolates could have serious therapeutic consequences. SIGNIFICANCE AND IMPACT OF STUDY: The molecular subtyping and the further characterization of these isolates may be valuable particularly in the context of a suspected common source outbreak in the future.

Refinement of the Region for Split Hand/Foot Malformation 5 on 2q31.1.

Background: Deletions that encompass 2q31.1 have been proposed as a microdeletion syndrome with common clinical features, including intellectual disability/developmental delay, microcephaly, cleft palate, growth delay, and hand/foot anomalies. In addition, several genes within this region have been proposed as candidates for split hand-foot malformation 5 (SHFM5). Methods: To delineate the genotype-phenotype correlation between deletions of this region, we identified 14 individuals with deletions at 2q31.1 detected by microarray analysis for physical and developmental disabilities. Results: All subjects for whom detailed clinical records were available had neurological deficits of varying degree. Seven subjects with deletions encompassing the HOXD cluster had hand/foot anomalies of varying severity, including syndactyly, brachydactyly, and ectrodactyly. Of 7 subjects with deletions proximal to the HOXD cluster, 5 of which encompassed DLX1/DLX2, none had clinically significant hand/foot anomalies. In contrast to previous reports, the individuals in our study did not display a characteristic gestalt of dysmorphic facial features. Conclusion: The absence of hand/foot anomalies in any of the individuals with deletions of DLX1/DLX2 but not the HOXD cluster supports the hypothesis that haploinsufficiency of the HOXD cluster, rather than DLX1/DLX2, accounts for the skeletal abnormalities in subjects with 2q31.1 microdeletions.

Psychosocial adjustment to diabetes-related lower limb amputation.

AIM: To examine psychosocial adjustment in persons with lower limb amputations related to diabetes. METHODS: Thirty-eight participants with diabetes-related lower limb amputations, recruited from two limb-fitting centres, completed three psychological self-report assessments: the Trinity Amputation and Prosthesis Experience Scales (TAPES); the Hospital Anxiety and Depression Scale (HADS); and the Amputation Body Image Scale-Revised (ABIS-R). RESULTS: Over 18% of participants scored above the normal range (> 8) for depression on the HADS and 18.5% scored above the normal range for anxiety. Both depression (rho = 0.75, P < 0.01) and anxiety (rho = 0.62, P < 0.01) scores were significantly associated with body image disturbance, as measured using the ABIS-R. Significant relationships were also observed between body image disturbance and three TAPES subscales measuring psychosocial adjustment [general adjustment (rho = -0.48, P < 0.01), social adjustment (rho = -0.51, P < 0.01), adjustment to limitations (rho = -0.45, P < 0.05)]. CONCLUSIONS: Individuals with diabetes-related amputations may be at elevated risk for psychological distress as a result of their co-morbid medical condition. Regular screening for anxiety and depression and the provision of appropriate follow-up care may therefore be advisable in this population.

Long-term survival of nonhuman primate islets implanted in an omental pouch on a biodegradable scaffold.

The aim of this study was to test whether an omental pouch can be used as an alternative site for islet implantation in diabetic monkeys. Here we report the successful engraftment of islets in diabetic cynomolgus monkeys when loaded on a synthetic biodegradable scaffold and placed in an omental pouch. One autologous and five allogeneic diabetic monkey transplants under the cover of steroid-free immune suppression (SFIS) were undertaken. Fasting blood glucose (FBG) and C-peptide (CP), exogenous insulin requirements (EIR), intravenous glucose tolerance test (IVGTT), A1C and histopathology were used to assess islet engraftment and survival. All animals achieved CP levels > 1.0 ng/mL following transplant, a 66-92% posttransplant decrease in EIR and reduced A1C. Following graft removal, CP became negative and histopathological analysis of the explanted grafts demonstrated well-granulated and well-vascularized, insulin-positive islets, surrounded by T-cell subsets and macrophages. Compared to intrahepatic allogeneic islet transplants (n = 20), there was a delayed engraftment for omental pouch recipients but similar levels of CP production were ultimately achieved, with a broad range of IEQ/kg transplanted in both sites. Our results suggest this extrahepatic transplantation site has potential as an alternative site for clinical islet cell transplantation.

Quantification of the coupled motion that occurs with axial rotation and lateral bending of the head-neck complex: an experimental examination.

The vertebrae of the cervical spine exhibit out-of-plane or coupled motion during axial rotation and lateral bending. Quantifying the range of motion (ROM) of this occurrence can aid the understanding of cervical spine injury mechanisms and disorders, as well as the development of new treatment methods. Previous studies have formulated ratios to describe coupled motion obtained from in-vitro examinations. The aim of the present study was to use in-vivo test data to develop mathematical relationships to quantify the coupled motion that occurs with axial rotation and lateral bending of the head-neck complex. Using a three-dimensional motion analyser it was possible to trace the coupling effect throughout the full range of unrestricted head-neck motion. Values for primary and coupled ROMs were obtained, showing no significant difference between male and female primary ROMs but a small disparity between male and female coupled ROMs. Regression equations were found to quantify coupled motion throughout the range of axial rotation and lateral bending. The present experimental study also examines the range of horizontally fixed axial rotation of the head to determine the minimum amount of coupled lateral bending that takes place, which has not been measured previously.

Persistence of strong electron coupling to a narrow boson spectrum in overdoped Bi2Sr2CaCu2O(8+delta) tunneling data.

A d-wave, Eliashberg analysis of break-junction and STM tunneling spectra on Bi2Sr2CaCu2O(8+delta) (Bi2212) reveals that the spectral dip feature is directly linked to strong electronic coupling to a narrow boson spectrum, evidenced by a large peak in alpha2F(omega). The tunneling dip feature remains robust in the overdoped regime of Bi2212 with bulk T(c) values of 56 K-62 K. This is contrary to recent optical conductivity measurements of the self-energy that suggest the narrow boson spectrum disappears in overdoped Bi2212 and therefore cannot be essential for the pairing mechanism. The discrepancy is resolved by considering the way each technique probes the electron self-energy, in particular, the unique sensitivity of tunneling to the off-diagonal or pairing part of the self-energy.

Can the radiologist accurately predict the adequacy of sampling when performing ultrasound-guided core biopsy of BI-RADS category 4 and 5 lesions detected on screening mammography?

AIM: To investigate in mammography screening the correlation between the confidence level of the radiologist, in sampling BI-RADS assessment category 4 and 5 lesions using a single ultrasound-guided 14-gauge needle core biopsy, and the final histological diagnosis. METHODS: In a prospective study, 389 consecutive ultrasound-guided 14-gauge needle core biopsies were performed on 131 BI-RADS assessment category 4 and 5 breast lesions in 126 women. On average, 3 passes were made through each lesion; for each pass, the radiologist rated confidence in adequacy of sampling at <50%, 50% to 90% or >90%. This was compared with the final histological diagnosis. RESULTS: The radiologist was >90% confident in 293 biopsies; diagnostic results were confirmed at histology in 283 (97%). In 70 biopsies the radiologist was 50% to 90% confident; diagnostic results were confirmed in 60 (86%). Of 26 samples where confidence was <50%, 13 were diagnostic (50%) (p<0.0001). CONCLUSION: If, at the time of ultrasound-guided needle core biopsy of BI-RADS assessment category 4 and 5 breast lesions, the radiologist is >90% confident that the lesion has been adequately sampled, a single pass is usually sufficient for diagnosis.

Nightly home hemodialysis: improvement in nutrition and quality of life.

In September, 1997, we began a Nightly Home Hemodialysis Program modeled after a program in Toronto, Canada. We have assessed nutritional parameters and quality of life indicators before initiation of the program, and at 3, 6, 12, and 18 months. Data suggest that patients have improved overall quality of life as measured by the CHOICE Health Experience Questionnaire. Three-day dietary recalls at 0, 3, 6, 12, and 18 months also show patients are eating healthy and maintaining adequate kilocalorie and protein intakes, as well as maintaining adequate dry weight and protein stores.

Potent and selective ligands for the dopamine transporter (DAT): structure-activity relationship studies of novel 4-[2-(diphenylmethoxy)ethyl]-1-(3-phenylpropyl)piperidine analogues.

Molecular structural modifications of 4-[2-(diphenylmethoxy)ethyl]-1-(3-phenylpropyl)piperidine (1a), a dopamine transporter (DAT)-specific ligand, generated several novel analogues. Biological activities of these new molecules for their binding to the DAT and serotonin transporter (SERT) were evaluated in rat striatal membranes. Some of these new analogues were more potent and selective than GBR 12909 when their binding to the DAT relative to SERT was compared. Thus compounds 9 and 19a were among the most potent (IC50 = 6.6 and 6.0 nM, respectively) and selective (DAT/SERT = 33.8 and 30.0, respectively) compounds in this series, and they were more active than GBR 12909 (IC50 = 14 nM, DAT/SERT = 6.1). Introduction of a double bond in the N-propyl side chain of these molecules did not influence their activities to a great extent. Bioisosteric replacement of the aromatic phenyl group by a thiophene moiety produced some of the most potent compounds in this series.

Cations affect [3H]mazindol and [3H]WIN 35,428 binding to the human dopamine transporter in a similar fashion.

The present study addresses the possibility that there are different cocaine-related and mazindol-related binding domains on the dopamine transporter (DAT) that show differential sensitivity to cations. The effects of Zn2+, Mg2+, Hg2+, Li+, K+, and Na+ were assessed on the binding of [3H]mazindol and [3H]WIN 35,428 to the human (h) DAT expressed in C6 glioma cells under identical conditions for intact cell and membrane assays. The latter were performed at both 0 and 21 degrees C. Zn2+ (30-100 microM) stimulated binding of both radioligands to membranes, with a relatively smaller effect for [3H]mazindol; Mg2+ (0.1-100 microM) had no effect; Hg2+ at approximately 3 microM stimulated binding to membranes, with a relatively smaller effect for [3H]mazindol than [3H]WIN 35,428 at 0 degrees C, and at 30-100 microM inhibited both intact cell and membrane binding; Li+ and K+ substitution (30-100 mM) inhibited binding to membranes more severely than to intact cells; and Na+ substitution was strongly stimulatory. With only a few exceptions, the patterns of ion effects were remarkably similar for both radioligands at both 0 and 21 degrees C, suggesting the involvement of common binding domains on the hDAT impacted similarly by cations. Therefore, if there are different binding domains for WIN 35,428 and mazindol, these are not affected differentially by the cations studied in the present experiments, except for the stimulatory effect of Zn2+ at 0 and 21 degrees C and Hg2+ at 0 degrees C.

Regulation of the functional activity of the human dopamine transporter by protein kinase C.

The role of protein kinase C (PKC) was examined in the regulation of dopamine transport in C6 glioma cells stably expressing the human dopamine transporter. The PKC activating phorbol esters phorbol 12-myristate 13-acetate (PMA) and 4 beta-12,13-dibutyrate phorbol-ester (PDBu) inhibited [3H]dopamine uptake concentration dependently. These effects were attenuated by the PKC inhibitor staurosporine but were unaltered by another inhibitor, chelerythrine, or the phosphatase inhibitor okadaic acid. The potency of PMA in inhibiting [3H]dopamine uptake was similar to that in inhibiting the binding of 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane ([3H]WIN 35,428), and again staurosporine, but not chelerythrine, weakened the effect of PMA. The reduction in dopamine transporter activity by PMA was caused by a decrease in the Vmax value of [3H]dopamine uptake, opposed by a smaller reduction in the Km value, whereas the effect of PMA on [3H]WIN 35,428 binding was caused by a reduction in the Bmax value without a change in the Kd value. The lower Km value in the presence of PMA was accompanied by a higher IC50 of dopamine in inhibiting [3H]WIN 35,428 binding; the latter effect was attenuated by the co-presence of staurosporine. The results are discussed in the context of transporter loss from the cell surface, or a model with phosphorylation affecting the shared dopamine and WIN 35,428 binding domain on the transporter as well as affecting a part of the dopamine binding domain lying outside that for WIN 35,428.

Highly selective, novel analogs of 4-[2-(diphenylmethoxy)ethyl]- 1-benzylpiperidine for the dopamine transporter: effect of different aromatic substitutions on their affinity and selectivity.

Several analogs of the potent and selective dopamine transporter (DAT) ligand 4-[2-(diphenylmethoxy)ethyl]-1-benzylpiperidine, 1a, were prepared and biologically evaluated at the dopamine and serotonin transporter (SERT) sites. Several substituents were introduced in the aromatic rings to evaluate the influences of electronic and steric interactions in their binding to the DAT. All the novel analogs showed preferential interaction at the DAT compared with the SERT. Different aromatic substitutions in the phenyl ring of the N-benzyl part of the molecule played a key role in the selectivity. In general, compounds with strong electron-withdrawing substituents were most active and selective at the DAT. Thus, compounds 5a (R = F) and 11b (R = NO2) were among the most potent (IC50 = 17.2 and 16.4 nM, respectively) and most selective (SERT/DAT = 112 and 108, respectively) and were far more selective than GBR 12909 (SERT/DAT = 6). Bioisosteric replacement of one of the phenyl rings of the diphenylmethoxy moiety by a thiophene ring was tolerated well and produced the most potent compound 13b (IC50 = 13.8 nM) in the series. Our current structure-activity studies of these piperidine analogs resulted in the generation of second generation of GBR-type compounds, and all of these new compounds reported here were more selective than GBR 12909 in interacting with the DAT over the SERT.

Binding domains for blockers and substrates on the dopamine transporter in rat striatal membranes studied by protection against N-ethylmaleimide-induced reduction of [3H]WIN 35,428 binding.

Binding sites for 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)[3H]tropane ([3H]WIN 35,428) on rat striatal membranes were alkylated with N-ethylmaleimide (NEM), and the protective potency was measured of the blockers cocaine, N[1-(2-benzo[b]thiophenyl) cyclohexyl]piperidine (BTCP), benztropine, WIN 35,428; and nomifensine, and of the substrates dopamine, norepinephrine, S(+)-amphetamine, tyramine, and metaraminol. In general, the protective potency was lower (at least 3 times) than the potency in inhibiting [3H]WIN 35,428 binding with the compounds present under the same experimental conditions used for the NEM-induced alkylation. However, the disparity was substantially greater for all substrates tested (10- to 93-fold) than for the blockers (2- to 6-fold), especially cocaine and BTCP (3-fold). [3H]WIN 35,428 binding was best described by a l-site model under the present conditions. The results are discussed in terms of models involving blocker-induced conformational changes and overlapping nonidentical binding domains for blockers and substrates.

Binding domains for blockers and substrates on the cloned human dopamine transporter studied by protection against N-ethylmaleimide-induced reduction of 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)[3H]tropane ([3H]WIN 35,428) binding.

Binding sites for 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)[3H]tropane ([3H]WIN 35,428) on the human dopamine transporter expressed in C6 glioma cells were alkylated with N-ethylmaleimide (NEM), and the protective potency of the blockers cocaine, N[1-(2-benzo[b]thiophenyl) cyclohexyl]piperidine (BTCP), and benztropine, and of the substrates dopamine, d-amphetamine, and norepinephrine was measured. In general, the protective potency was lower (at least 4-5 times) than the potency in inhibiting [3H]WIN 35,428 binding with the compounds present under the same experimental conditions used for the NEM alkylation. However, the disparity was substantially greater for all substrates tested (23- to 44-fold) than for the blockers (4- to 11-fold), especially cocaine (5-fold) and BTCP (4-fold). Benztropine took an intermediate place (11-fold) between cocaine (5-fold) and BTCP (4-fold), on the one hand, and dopamine (23-fold), on the other hand. [3H]WIN 35,428 binding was best described by a one-site model under the present conditions. The results are discussed in terms of models involving blocker-induced conformational changes and overlapping nonidentical binding domains for blockers and substrates.