Search

An analytical method is proposed for the estimation of gain enhancement in superstrate-loaded microstrip patch antenna, when its dielectric substrate and superstrate are replaced by air. The validity of the proposed analytical model is verified over different physical dimensions of the antenna. Analysis is carried on a rectangular microstrip patch antenna and a hexagonal microstrip patch with various combinations of air and dielectric materials as substrate and superstrates. Rectangular microstrip patch antenna etched on dielectric substrate and loaded with superstrate resonates at 1.67GHz and the same antenna resonates at 2.97GHz when both the dielectrics are replaced with air. Similarly the rectangular microstrip patch resonates at 2.41 GHz when only the substrate is replaced with air and resonates at 1.8 GHz when the superstrate is replaced with air. The hexagonal microstrip patch antenna resonates at 3.9GHz when it is etched on dielectric substrate and loaded with dielectric superstrate. By replacing both dielectric substrate and superstrate with air the hexagonal microstrip patch antenna resonates at 8.3GHz. Similarly, when the substrate is alone replaced with air the hexagonal microstrip patch antenna resonates at 6.7GHz. The hexagonal microstrip patch antenna resonates at 4.3GHz when the superstrate is alone replaced with air. The antenna's performance evaluation is done at their respective resonant frequencies. Alternatively Finite element method based 3D simulator is utilized to calculate the gain enhancement. Both the theoretical and simulation results are comparable with the proposed analytical model.

A compact 2-port multiple input multiple output (MIMO) antenna system with fractal shaped antenna elements of total size 17×40 mm2 is proposed for WiMax/WLAN applications. The physical separation between the antenna elements of the proposed system is 0.15λ (λ being the free-space wavelength at 5.4 GHz). The two antenna elements are orthogonally placed and the MEMO system exhibits pattern diversity with high isolation, without additional structures for isolation improvement. The performance of the antenna is studied in terms of S-parameter, radiation pattern and envelope correlation coefficient. The measured results show that the relative bandwidth of the proposed antenna is 1.2 GHz (4.8 – 6 GHz) with S11 ≤ −10dB, S11 ≤ −20dB and envelope correlation coefficient (ECC) < 0.01. The proposed MEMO system is believed to be a good candidate for high density packaged MIMO system.

In this paper, a compact 2-element ultra wideband MIMO antenna system measuring 20×32 mm2 is proposed. The radiating element of the monopole antenna configuration is fractal shaped, and is fed by a coplanar waveguide independently. A T-shaped reflecting stub is placed between the two antennas to reduce mutual coupling and hence to improve isolation. The antenna performance is studied in terms of impedance matching, isolation, radiation pattern, and Envelope Correlation Coefficient (ECC). The measured result shows that the proposed antenna operates in the UWB frequency range of 3.1–7.5 GHz with S11 ≤ −10dB (S11 ≤ −8dB for 7.5–10.6 GHz) and S21 ≤ −15dB. The antenna exhibits an ECC of less than 0.06. The proposed antenna configuration provides beam tilting over the operating frequency due to the presence of the T-shaped stub, thus creating pattern diversity.

A compact reduced unit cell size electromagnetic bandgap (EBG) power plane, realized with a combination of alternating impedance EBG and multiple narrow slits, is presented. By concatenating 2 × 2 high-frequency unit cells, a virtual low-frequency EBG unit cell is synthesized without changing the overall dimensions. In this configuration, the basic slit in the high-frequency unit cell remained same, and an additional slit with longer dimensions is added in parallel to the basic slit by synthesizing a larger low-frequency unit cell. EBG is characterized for its dispersion diagram, noise suppression, signal integrity, and electromagnetic radiation. Fabricated EBG exhibits a bandgap from 0.9 to 3.5 GHz with isolation better than -40 dB over the band. Radiated emission of the new EBG is small with an average value of 35 dB·uV/m. Compact EBG also exhibits low impedance, which is less than 1 Ω over the stopband. Eye patterns are generated to analyze signal integrity issues when the data lines are referenced over the solid ground plane and EBG plane. The degradation of the maximum eye opening and the maximum eye width for the proposed EBG power plane at 2 Gb/s data rate is about 17.8% and 1%, respectively, with reference to the equivalent board with solid power plane.

A compact reduced size electromagnetic bandgap (EBG) structure with multiple narrow slits unitcell is presented. The new EBG structure is realized with a combination of alternating impedance EBG and multiple narrow slits in power plane. By concatenating 2 × 2 high frequency unitcells, a virtual low frequency EBG unitcell is created without changing the overall dimensions. In this configuration, the basic slit in the high frequency unitcell remained same and an additional Z-slit is added in parallel to the basic slit with larger dimensions by synthesizing a larger unitcell. This new configuration provides low onset frequency and wideband noise suppression with small unitcell dimensions. Measured and simulated results show noise suppression and isolation over 50 dB in most of the stop-band (0.7-3.5 GHz) and also exhibit low impedance, which is less than 1 Ω over the stop-band. Eye patterns are generated for analyzing signal integrity referenced to the solid power/ground plane and EBG plane. Maximum eye opening (MEO) and the maximum eye width (MEW) analyzed for the signal on EBG reference plane are presented and compared. The degradation of the MEO and MEW for the proposed EBG board is about 16.2 and 1%, respectively, with reference to the equivalent board with solid power plane.

Carboxymethyl cellulose (CMC) is a kind of cellulose ether widely used in industrial production. CMC wastewater usually have high chemical oxygen demand (COD) and salinity (>10 %), which result from organic and inorganic by-products during CMC production. It is significant that the wastewater is pretreated to decrease salinity and recover valuable organics before biochemical methods are employed. In this paper, distillation-extraction method was used to pretreat CMC wastewater and recover valuable chemical compounds from wastewater (Fig. 1). Initial pH of CMC wastewater was adjusted to different values (6.5, 8.5, 9.5, 10.5, 12.0) before distillation to study the effect of pH on by-products in wastewater. By-products obtained from CMC wastewater were extracted and characterized by NMR, XRD and TGA. Distillate obtained from distillation of wastewater was treated using biological method, i.e., upflow anaerobic sludge blanket (UASB)-contact oxidation process. Domestic sewage and flushing water from manufacturing shop was added into distillate to decrease initial COD and increase nutrients such as N, P, K. Experimental results showed that by-products extracted from CMC wastewater mainly include ethoxyacetic acid and NaCl, which were confirmed by NMR and XRD (Fig. 2). TGA results of by-products indicated that the content of NaCl in inorganic by-products reached 96 %. Increasing initial pH value of CMC wastewater might significantly raise the purity of ethoxyacetic acid in organic by-products. UASB-contact oxidation process showed a good resistance to shock loading. Results of 45-day continuous operation revealed that CODCr of final effluent might be controlled below 500 mg l−1 and meet Shanghai Industrial Wastewater Discharge Standard (CODCr < 500 mg l−1), which indicated that the treatment process in this study was appropriate to treat distillate of wastewater from CMC production industry., Otpadne vode s karboksimetil-celulozom (CMC) obično imaju visoku kemijsku potrebu za kisikom (COD) i salinitet (> 10 %). Prije primjene biokemijskih metoda važno je otpadne vode pročistiti radi smanjenja saliniteta i oporabe vrijednih spojeva. U ovom je radu otpadna voda s CMC-om predobrađena destilacijom i ekstrakcijom. Iz otpadne vode izvučeni su vrijedni kemijski spojevi uključujući etoksioctenu kiselinu i NaCl. Analize metodama GC-MS i NMR pokazuju da čistoća etoksioctene kiseline raste s povećanjem početnog pH otpadne vode. Primijenjen je anaerobno-aerobni postupak za pročišćavanje destilata (reaktor s lebdećim muljem i kontaktna oksidacija), koji je pokazao dobru otpornost na udarna opterećenja. Nakon 45-dnevnog kontinuiranog rada CODCr se može održati ispod 500 mg l−1 što je u skladu sa šangajskim standardima za ispuštanje industrijskih otpadnih voda.

Persons with mental illnesses in India and rest of developing world continue to consult religious/spiritual (R/S) healers or traditional, complementary and alternative medicine (TCAM) professionals prior to seeking psychiatric services that are devoid of spiritual components of care. We aim to understand TCAM and allopathic professionals’ perspectives on patients’ R/S needs within mental health services, cross-sectional study was conducted at five TCAM and two allopathic tertiary care hospitals in three different Indian states; 393 participants completed RSMPP, a self-administered, semi-structured survey questionnaire. Perspectives of TCAM and allopathic health professionals on role of spirituality in mental health care were compared. Substantial percentage, 43.7 % TCAM and 41.3 % allopathic, of participants believe that their patients approach R/S or TCAM practitioners for severe mental illness; 91.2 % of TCAM and 69.7 % of allopaths were satisfied with R/S healers (p = 0.0019). Furthermore, 91.1 % TCAM and 73.1 % allopaths (p = 0.000) believe that mental health stigma can be minimized by integrating with spiritual care services. Overall, 87 % of TCAM and 73 % of allopaths agreed to primary criterion variable: ‘spiritual healing is beneficial and complementary to psychiatric care.’ A quarter of allopaths (24.4 %) and 38 % of TCAM physicians reportedly cross-refer their grieving patients to religious/TCAM healer and psychiatrist/psychologist, respectively; on logistic regression, significant (p

A broadband fractal slot coupled stacked microstrip antenna is presented. Third order fractal slots are used, to improve the antenna bandwidth. The antenna resonates at the center frequency of 1.5GHz and offers 30% bandwidth for a return loss criterion of 10dB. The introduction of fractal slot also leads to antenna miniaturization. The proposed configuration is fabricated and characterized for gain, return loss and radiation patterns. While the measured peak gain of the fractal slot coupled antenna configuration is 8 dB at the center frequency, an average gain of 7dB is measured over the band.

A simple and compact planar printed monopole antenna for ultra wideband application is presented. The proposed antenna comprising of bevel slots in the lower parts of the antenna with annular ring slot. Partial ground plane has been used to enhance the impedance bandwidth. The simulated results show that the proposed antenna exhibits UWB for 2.7 GHz to 11.22 GHz with -10dB return loss and VSWR

The effects of corporate feed network on the performance of low sidelobe level (SLL) planar array operating in X-band are analyzed. The impedance distribution at the individual sub-arrays is optimized to suppress the effects of corporate feed radiation and to achieve the required low sidelobe level (∼20dB). Conventional planar feed design exhibited a distorted radiation pattern with second sidelobe level shooting upto −14dB. The proposed approach reduces the second sidelobe level and maintains nearly Gaussian tapered radiation pattern over the angle. Measured gain of the array is 21dB.

Analysis of electromagnetic noise mitigation in a mixed signal board consisting of analog to digital convertor (ADC) and low noise amplifier (LNA) is presented. A new approach of mitigating the electromagnetic noise is proposed in the form of complementary split ring resonator (CSRR) loaded right handed (RH) transmission line as an alternative to EBG loaded large power planes. To analyze the effect of electromagnetic noise in mixed signal board, noise coupling power and noise figure at the output of LNA were measured for various periodic configurations (RH transmission line, alternating impedance electromagnetic bandgap (AIEBG), and CSRR loaded transmission line). The noise figure at the output of LNA is 11.5 dB, 2.9dB and 2.7 dB for RH transmission line, AIEBG based power plane and CSRR loaded RH transmission line respectively.

Analysis of phase characteristics of a transmission lines with capacitive stubs loaded with CSRRs of three different geometries (square, circle and triangle) in the ground plane is presented. The phase delays of −270°, −267° and −263° are observed for CSRRs of square, circular and triangular geometries respectively at resonant frequency of 1.75GHz compared with a reference transmission line (0deg) of same length. A length reduction of approximately 75% is achieved for all three CSRR loaded transmission lines when compared with a conventional transmission line.

It is known that complementary split ring resonators (CSRR) can be used for reducing the size of microwave circuits. In this paper, the length of the 90° branch line in L-Band power divider is reduced by implementing the CSRR in the ground plane underneath the branch line. The overall reduction in foot print of the proposed approach is 37% when compared to the conventional power divider. The power divider operates from 1.65 GHz to 1.8GHz, with nearly equal power division of 3.4dB. The measured isolation between the output ports is 22.73dB.

The reconfigurability of phase delay in a complementary split ring resonator (CSRR) loaded microstrip transmission line with capacitive stubs is presented. The reconfigurable phase delay is achieved by varying the short positions on the CSRR. A linear increment in the phase delay is obtained by varying the short positions of the inner ring of the CSRR. Five distinct phase delays are obtained for different positions of the short with a maximum phase delay of −340°. The phase delays generated by the Left Handed phase delay line fall within a range between −340.32° and −308.97° when compared to a reference transmission line.

Combined cytogenetic, chromosome painting, and spectral karyotyping (SKY) analyses in a case of hepatoblastoma revealed a karyotype of 49,XY,+Y,+der(2)t(2;3)(q35;q25),der(3)t(1;3)(q12; q25),+20. Trisomy 1q, 2, and 20 identified in the present case are consistent with the previously reported cytogenetic alterations in hepatoblastoma. The breakpoints at 1q12 and 2q35 identified in this case have also been reported previously as nonrandom changes. The frequent occurrence of these rearrangements in hepatoblastoma suggests that they may be of pathogenic significance.

In this paper, a new configuration of UWB planar printed compact monopole antenna has been presented. The proposed antenna comprising of U-shaped notch loaded with tuning stubs and annular ring slot. It has a partial ground plane to achieve an excellent impedance matching to increase the impedance bandwidth. The simulated results show that the proposed antenna exhibits UWB for 4.32 GHz to 12.92 GHz with -10dB return loss and VSWR

In this paper, a new configuration of UWB planar printed compact monopole antenna comprising of symmetrical slots and PI notched with parasitic patches. It has a partial ground plane to achieve an excellent impedance matching to increase the impedance bandwidth. The proposed antenna rejects the 5GHz WLAN band in the frequency range of 5.42-5.74 GHz by introducing PI shaped notch. The simulated results show that the proposed antenna exhibits UWB for 3.52 GHz to 11.06 GHz with -10dB return loss and VSWR

This paper presents an UWB planar printed compact monopole antenna comprising of U-shaped notch loaded with L-slot and tuning stubs. It has a partial ground plane to achieve an excellent impedance matching to increase the impedance bandwidth. The simulated results show that the proposed antenna exhibit UWB for 3.84 GHz to 11.61 GHz with –10dB return loss and VSWR < 2. Antenna gain and radiation pattern plots for different frequencies are also investigated. The performance characteristics of the proposed antenna are simulated using Ansoft HFSS software. Index Terms planar antenna, ultra wideband, partial ground plane.

The t(9;14)(p13;q32) translocation is associated with approximately 50% of lymphoplasmacytoid lymphoma (LPL), a subtype of B-cell non-Hodgkin's lymphoma (NHL). We cloned the chromosomal breakpoint of der (14) from an LPL case (1052) and showed that it involved a junction between 9p13 and the switch micro region of the Ig heavy chain locus (IgH) on 14q32. Using a YAC contig spanning 1.5 megabase (Mb), we determined that the 9p13 breakpoint in one case (1052) mapped within a 270-kb restriction fragment containing two previously reported 9p breakpoints associated with a alpha-heavy chain disease case (MAL) and KI-1 positive diffuse large cell lymphoma (DLCL) cell line (KIS-1). The same fragment also contained the PAX-5 gene which encodes a B-cell specific transcription factor involved in the control of B-cell proliferation and differentiation. The breakpoints of KIS-1 and 1052 were mapped within the 5′ noncoding region of PAX-5, while the 9p13 breakpoint of MAL mapped 230 to 270 kb upstream to PAX-5. In all three cases, the translocation caused the juxtaposition of the PAX-5 gene to the IgH locus in the opposite direction of transcription. When compared with six other DLCL cell lines lacking t(9;14)(p13;q32), the KIS-1 cell line showed an 11-fold overexpression of PAX-5 mRNA and a significantly reduced expression of the p53 gene, which is normally regulated by PAX-5. Moreover, metaphase and interphase fluorescence in situ hybridization (FISH) analysis using a YAC clone spanning 1 Mb including the PAX-5 as a probe identified chromosomal translocations in 5 of 7 cases carrying 9p13 translocations. These findings suggest that the PAX- 5 gene is the target of the t(9;14) in LPL whereby its expression may be deregulated by juxtaposition to IgH regulatory elements, thus contributing to lymphomagenesis.

Design of two element printed crank-line array is presented as an inverted microstrip line structure. High gain circularly polarized (CP) tilted beam is achieved from this configuration. The antenna consists of crank-line element as a travelling wave radiator and fed with a printed Z-feed with a printed vertical stub termination. A microstrip power divider is employed to feed array elements with equal amplitude and quadrature phase difference to tilt the main beam direction to 410. Power divider and radiating elements both share the common ground. The antenna exhibits an impedance bandwidth of 43% (3.58-5.3 GHz) for a VSWR

A circularly polarized (CP) printed slot antenna configuration on a shared aperture is proposed. Antenna is designed to operate at two distinct frequency bands of 4GHz and 8GHz. Dual slot CP elements at two frequencies are created on a common shared aperture and the antenna is fed by a single microstrip feed line. To achieve unidirectional beam, the slot antenna is backed by a stepped reflector. The stepped reflector is optimized to provide proper phase for pattern combining and axial ratio improvement at both the frequency bands. Antenna operates over a frequency range of 3.5 to 4.5GHz and 7.5 to 8.5GHz for a VSWR

A microstrip antenna couplet on a periodic patterned ground plane is proposed to provide circularly polarized tilted beam. Circular polarization is achieved by employing two wide microstrip antenna elements designed to operate in C-band. The elements are fed at the corners with 900 phase difference along a travelling wave microstrip feed line. A novel concept of patterned slotted ground plane is utilized in tilting the main beam from the broadside. The slot patterns on the ground plane and the dimensions of microstrip patches and their angle with respect to the feed line are optimized to achieve wideband axial ratio. The designed antenna exhibits a maximum gain of 3.2dB with beam pointing angle at 300 and operates over a bandwidth of around 8% for a VSWR

An Ultra Wideband (UWB) monopole antenna on a shaped ground plane is presented. This compact and thin antenna operates from 3.1 to 10.6 GHz. The radiating element is created by stitching the conductive thread instead of the copper metallization. The ground plane is created by using a Liquid Crystal Polymer (LCP)material(e r=2.9). The substrate of the designed antenna is made from jeans fabric (e r=1.7) while the radiating element is made from stainless steel coated conductive thread. By changing the shaped ground, the direction of the radiation pattern can be changed. Radiation pattern is steered over an angle of 60 degrees on the both the sides of beam pointing angle.

Electromagnetic shielding for an electronic circuit is of prime concern in its design. With exponentially growing technology of VLSI; the circuit size is drastically reduced. Developing an electromagnetic shield for such a reduced size of electronic circuits requires ultra thin conductor shields while achieving the required shielding performance. Single conductor layer shield has thickness limitations to achieve required shielding effectiveness. Multilayered conductor electromagnetic shields are developed in this work so as to achieve the required performance of shielding effectiveness at lower thickness values. Mathematical analysis is carried out for a multilayered conductor electromagnetic shield. Conducting materials like copper, aluminum, silver, steel, nickel etc are considered for different layers of the shield at different thicknesses. Estimations for shielding effectiveness of a three layered (two layers of micro thin conductor films on a base conductor) conductor electromagnetic shield were carried out in different frequency ranges for various combinations of conductor layer materials. The combinations of conductor materials and their thicknesses were optimized to yield maximized performance at a reduced layer thickness.

La -modified ZnO nanosheet-assembled flower-like microstructures, were successfully obtained through a facile two-step solution-based strategy including a simple aqueous solution and subsequent impregnation technique. Scanning electron microscopy (SEM), X-ray diffraction (XRD) and ultraviolet-visible spectrometer (UV-Vis) were employed to characterize the morphology, composition, crystal structure and photocatalytic properties of prepared products in detail. The photocatalysis test results revealed that the La -modified ZnO nanoflowers displayed greatly enhanced catalytic performance and the decomposition efficiency was up to about 99.60%, which was mainly ascribed to the increased charge separation rate on the La -modified surface of ZnO nanosheets and the high surface area of the flower-like structure.

We applied a combination of molecular cytogenetic methods, including comparative genomic hybridization (CGH), spectral karyotyping (SKY), and fluorescence in situ hybridization, to characterize the genetic aberrations in a panel of 11 cell lines derived from head and neck squamous cell carcinoma and 1 cell line derived from premalignant oral epithelium. CGH identified recurrent chromosomal losses at 1p, 3p, 4, 8p, 10p, and 18q; gains at 3q, 5p, 8q, 9q, and 14q; and high-level amplification at 3q13, 3q25-q26, 5q22-q23, 7q21, 8q24, 11q13-q14, 12p13, 14q24, and 20q13.1. Several recurrent translocations including t(1;13)(q10;q10), t(13;13)(q10;q10), t(14;14)(q10;q10), i(8)(q10), and i(9)(q10) and breakpoint clusters at 1p11, 1q21, 3p11, 5q11, 5q13, 6q23, 8p11, 8q11, 9p13, 9q13, 10q11, 11q13, 13q10, 14q10, and 15q10 were identified by SKY. There was a good correlation between the number of aberrations identified by CGH and SKY (r = 0.69), and the analyses were both confirmatory and complementary in their assessment of genetic aberrations. Amplification at 3q26-q27 was identified in 42% of cases. Although SKY defined the derivation of 3q gain, the precise breakpoint remained unassigned. Positional cloning efforts directed at the amplified region at 3q26-q27 identified three highly overlapping nonchimeric yeast artificial chromosome clones containing the apex of amplification. The use of these yeast artificial chromosome clones as a probe for fluorescence in situ hybridization analysis allowed a detailed characterization and quantification of the 3q amplification and refinement of unassigned SKY breakpoints.

Combined cytogenetic, chromosome painting, and spectral karyotyping (SKY) analyses in a case of hepatoblastoma revealed a karyotype of 49,XY,+Y,+der(2)t(2;3)(q35;q25),der(3)t(1;3)(q12; q25),+20. Trisomy 1q, 2, and 20 identified in the present case are consistent with the previously reported cytogenetic alterations in hepatoblastoma. The breakpoints at 1q12 and 2q35 identified in this case have also been reported previously as nonrandom changes. The frequent occurrence of these rearrangements in hepatoblastoma suggests that they may be of pathogenic significance.

Combining degenerate oligonucleotide-primed PCR (DOP-PCR) with comparative genomic hybridization (CGH) has made it possible to analyze genomic changes in single cells. Although DOP-PCR-CGH methodology has been reported, the reproducibility of the method has been uncertain. We have developed a reproducible DOP-PCR-CGH protocol by systematically evaluating different labeling methods (including nick translation, PCR incorporation, and random-primed labeling) and different hybridization mixtures (including amplified test DNA vs. amplified reference DNA, termed homo-hybridization; and amplified test DNA vs. unamplified reference DNA or vice versa, termed hetero-hybridization). We have analyzed DNA samples obtained from 16 tissue sources including fresh/frozen normal and tumor samples, formalin fixed and paraffin embedded tumor tissue, and tumor cell lines by using differently labeled probes and hybridization combinations, and we calculated the corresponding rate (CR) of DOP-PCR-CGH with standard CGH. We found that homo-hybridization produced reproducible results with high CRs as compared to standard CGH (91-100% CR, mean 97%); In contrast, hetero-hybridization failed to generate reproducible hybridization with low CRs (57-97% CR, mean 80%; chi(2) = 1245.8, P0.0001), high background, uneven hybridization, and false deletions or amplifications. In addition, our improved DOP-PCR protocol raised the amplification efficiency at least five times as compared to previously reported protocols, allowing for the detection of genomic imbalances in as little as 12.5 pg of starting DNA. In conclusion, the DOP-PCR-CHG homo-hybridization method, especially when combined with labeling by nick translation, is reliable and reproducible. The method can be used in screening for genomic imbalances using minute amounts of tumor DNA, thereby facilitating CGH application. Genes Chromosomes Cancer 28:395-403, 2000.

Incorporation of Detarium Microcarpum (Dm) and Mucuna flagellipes (Mf) water soluble polysaccharides (gums) at 0.0 to 0.5% levels in wheat flour was studied to evaluate their effect on the rheological properties of wheat flour dough and white bread quality. At all levels of incorporation, there were increases (por = 0.05) in water absorption of the dough. Doughs containing gums had higher (por = 0.05) mixing tolerance index than the control. Set back viscosities decreased by 4.0 RVU and 9.0 RVU with increased levels of Dm and Mf gum incorporation, respectively. Significantly (por = 0.05) higher oven spring occurred in all the gum substituted white bread when compared to the control. The 0.5% gum substituted breads had a significantly (por = 0.05) higher sensory score for crumb grain, texture but lower (p0.05) crumb firmness than the control as determined instrumentally. Textural analysis after 5 days storage revealed that Dm and Mf gums improved moisture retention properties of the bread and reduced crumb firming tendency.

A patient with BCR/ABL negative myeloproliferative syndrome with a 46,XY,del(3)(q21), t(4;15)(p16;q24) karyotype is described. Fluorescence in situ hybridization performed with chromosomes 4 and 15 painting probes confirmed a novel reciprocal (4;15) translocation. The absence of crkl tyrosine phosphorylation, no activation of the abl kinase as measured by autophosphorylation, and a normal-size abl transcript suggest an alternative mechanism for leukemogenesis to that operative in Ph positive BCR/ABL positive chronic myeloid leukemia. A number of genes potentially relevant to tumorigenesis, some involving the ras signaling pathway, map to the 4p16 and 15q24 chromosome regions.

Chromosomal band 3q27 frequently engages in translocations with a number of sites within the genome, including those containing IG and other genes, during the development of B-cell lymphoma. The BCL6 gene, mapped at 3q27, is deregulated in these translocations and was isolated from a t(3;14)(q27;q32) translocation. It encodes a zinc-finger transcription repressor protein, which is expressed mainly in the germinal center (GC) B cells and plays a key role in GC development and T-cell-dependent immune response. BCL6 deregulation in 3q27 translocations is brought about by substitution of its 5' regulatory sequences by promoters of the rearranging genes. BCL6-rearranging genes studied so far (IGH, IGLL, TTF, BOBI, H4) displayed a broader pattern of expression than BCL6 during B-cell development. This observation has led to the suggestion that continued expression of BCL6 beyond its developmentally regulated point of downregulation under the direction of substituted promoters may keep the GC B cell in a cycling mode and lead to clonal expansion and lymphoma development. However, the rearranging partners of BCL6 in several of the 3q27 translocations have not yet been identified. In a molecular cloning analysis of two such translocations, t(1;3)(q21;q27) and t(3;6)(q27;p25), and an immunoblastic lymphoma cell line, OSI-LY8, we identified a novel mechanism of BCL6 deregulation. This comprised replacement of BCL6 5' regulatory sequences by insertion of IG gene transcriptional regulatory sequences at the translocation junction. These studies demonstrate novel features of instability of 3q27, and of the BCL6 and IGH genes, in B-cell lymphomagenesis.

Chromosomal translocations leading to deregulation of specific oncogenes characterize approximately 50% of cases of diffuse large B-cell lymphomas (DLBL). To characterize additional genetic features that may be of value in delineating the clinical characteristics of DLBL, we studied a panel of 96 cases at diagnosis consecutively ascertained at the Memorial Sloan-Kettering Cancer Center (MSKCC) for incidence of gene amplification, a genetic abnormality previously shown to be associated with tumor progression and clinical outcome. A subset of 20 cases was subjected to comparative genomic hybridization (CGH) analysis, which identified nine sites of chromosomal amplification (1q21-23, 2p12-16, 8q24, 9q34, 12q12-14, 13q32, 16p12, 18q21-22, and 22q12). Candidate amplified genes mapped to these sites were selected for further analysis based on their known roles in lymphoid cell and lymphoma development, and/or history of amplification in tumors. Probes for six genes, which fulfilled these criteria, REL (2p12-16), MYC (8q24), BCL2 (18q21), GLI, CDK4, and MDM2 (12q13-14), were used in a quantitative Southern blotting analysis of the 96 DLBL DNAs. Each of these genes was amplified (four or more copies) with incidence ranging from 11% to 23%. This analysis is consistent with our previous finding that REL amplification is associated with extranodal presentation. In addition, BCL2 rearrangement and/or REL, MYC, BCL2, GLI, CDK4, and MDM2 amplification was associated with advanced stage disease. These data show, for the first time, that amplification of chromosomal regions and genes is a frequent phenomenon in DLBL and demonstrates their potential significance in lymphomagenesis.

The molecular basis of parathyroid adenomatosis includes defects in the cyclin D1/PRAD1 and MEN1 genes but is, in large part, unknown. To identify new locations of parathyroid oncogenes or tumor suppressor genes, and to further establish the importance of DNA losses described by molecular allelotyping, we performed comparative genomic hybridization (CGH) on a panel of 53 typical sporadic (nonfamilial) parathyroid adenomas. CGH is a new molecular cytogenetic technique in which the entire tumor genome is screened for chromosomal gains and/or losses. Two abnormalities, not previously described, were found recurrently: gain of chromosome 16p (6 of 53 tumors, or 11%) and gain of chromosome 19p (5 of 53, or 9%). Losses were found frequently on 11p (14 of 53, or 26%), as well as 11q (18 of 53, or 34%). Recurrent losses were also seen on chromosomes 1p, 1q, 6q, 9p, 9q, 13q, and 15q, with frequencies ranging from 8-19%. Twenty-four of the 53 adenomas were also extensively analyzed with polymorphic microsatellite markers for allelic losses, either in this study (11 cases) or previously (13 cases). Molecular allelotyping results were highly concordant with CGH results in these tumors (concordance level of 97.5% for all informative markers/chromosome arms examined). In conclusion, CGH has identified the first two known chromosomal gain defects in parathyroid adenomas, suggesting the existence of direct-acting parathyroid oncogenes on chromosomes 16 and 19. CGH has confirmed the locations of putative parathyroid tumor suppressor genes, also defined by molecular allelotyping, on chromosomes 1p, 6q, 9p, 11q, 13q, and 15q. Finally, CGH has provided new evidence favoring the possibility that distinct parathyroid tumor suppressors exist on 1p and 1q, and has raised the possibility of a parathyroid tumor suppressor gene on 11p, distinct from the MEN1 gene on 11q. CGH can identify recurrent genetic abnormalities in hyperparathyroidism, especially chromosomal gains, that other methods to not detect.

The t(9;14)(p13;q32) translocation is associated with approximately 50% of lymphoplasmacytoid lymphoma (LPL), a subtype of B-cell non-Hodgkin's lymphoma (NHL). We cloned the chromosomal breakpoint of der (14) from an LPL case (1052) and showed that it involved a junction between 9p13 and the switch micro region of the Ig heavy chain locus (IgH) on 14q32. Using a YAC contig spanning 1.5 megabase (Mb), we determined that the 9p13 breakpoint in one case (1052) mapped within a 270-kb restriction fragment containing two previously reported 9p breakpoints associated with a alpha-heavy chain disease case (MAL) and KI-1 positive diffuse large cell lymphoma (DLCL) cell line (KIS-1). The same fragment also contained the PAX-5 gene which encodes a B-cell specific transcription factor involved in the control of B-cell proliferation and differentiation. The breakpoints of KIS-1 and 1052 were mapped within the 5' noncoding region of PAX-5, while the 9p13 breakpoint of MAL mapped 230 to 270 kb upstream to PAX-5. In all three cases, the translocation caused the juxtaposition of the PAX-5 gene to the IgH locus in the opposite direction of transcription. When compared with six other DLCL cell lines lacking t(9;14)(p13;q32), the KIS-1 cell line showed an 11-fold overexpression of PAX-5 mRNA and a significantly reduced expression of the p53 gene, which is normally regulated by PAX-5. Moreover, metaphase and interphase fluorescence in situ hybridization (FISH) analysis using a YAC clone spanning 1 Mb including the PAX-5 as a probe identified chromosomal translocations in 5 of 7 cases carrying 9p13 translocations. These findings suggest that the PAX-5 gene is the target of the t(9;14) in LPL whereby its expression may be deregulated by juxtaposition to IgH regulatory elements, thus contributing to lymphomagenesis.

Comparative genomic hybridization (CGH) analysis of DNA extracted from a diffuse lymphoma with a large cell component (DLLC) that displayed double minute chromosomes upon conventional karyotypic analysis indicated overt amplification of DNA sequences derived from the 2p13-15 region. Southern blot analysis of this tumor DNA with a cDNA probe for the proto-oncogene REL, previously mapped to 2p14-15, indicated a greater than 35-fold amplification of REL. To determine the incidence of REL amplification and possible clinical or histologic association with DLLC, a panel of 111 tumor DNAs from DLLC specimens was screened for REL amplification by Southern blot analysis. A copy number ofor = 4 was noted in 26 cases (23%). Southern blot analysis of these 26 tumor DNAs with a cDNA probe for TGFA, mapped to 2p13, indicated lack of coamplification except in one case. Another member of the Rel/NF-kappa B family of transcriptional activators, RELA/p65 mapped to 11q13, was amplified in five cases as determined by Southern blot analysis using a cDNA probe. Nineteen of the 26 DLLC (73%) with REL amplification were primary extranodal lymphomas. As a group, the tumors with REL amplification demonstrated an increased frequency of chromosomal aberrations previously associated with tumor progression, suggesting an oncogenic effect of amplified REL in B-lymphoid cells that already contained a transforming genetic lesion. Thus, REL amplification is a frequent event in DLLC, and probably constitutes a progression-associated marker of primary extranodal lymphomas. This study shows the usefulness of the CGH technique in identifying chromosomal regions overrepresented in tumors that can point to amplified genes and may be correlated with clinical features of the disease.

Two unique DNA fragments were recently identified in over 90% of acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma tissues. Sequence analysis suggests that these fragments belong to a previously unidentified human herpesvirus, Kaposi's sarcoma-associated herpesvirus (KSHV). These fragments have also been identified in a subset of non-Hodgkin's lymphomas in human immunodeficiency virus-positive patients; specifically, in body cavity-based lymphomas (AIDS-BCBLs). We have established two cell lines derived from AIDS-BCBLs, BC-1 and BC-2, which retain the KSHV sequences, and have used them to further characterize this putative viral genome. In this report, we demonstrate that the KSHV sequences represent a portion of a much larger DNA molecule that is located predominantly in the nucleus of the infected cells. In situ hybridization of metaphase spreads made from both of these cell lines show these sequences in episomal structures. Their presence in the cells as large nuclear episomes supports previous sequence homology data suggesting that KSHV belongs to the herpesvirus family. These cell lines provide a continuous source of KSHV sequences. Thus, they represent an important tool for future studies of this recently described human herpesvirus that may be involved in the pathogenesis of Kaposi's sarcoma and some AIDS-related non-Hodgkin's lymphomas.

The karyotypes of two recently developed cell lines derived from squamous cell carcinomas of uterine cervix have been analyzed and are described here. Several clonal rearrangements were identified in both cell lines. Abnormalities common to these two cell lines were i(5)(p10) and del(6)(q15q26). The i(5p) was confirmed by use of whole chromosome 5 painting probe in fluorescence in situ hybridization. Based on these findings and review of published data on the cytogenetics of carcinoma of uterine cervix these two lesions are considered to be nonrandom abnormalities associated with this tumor.

The results presented identify the first genetic lesion associated with DLCL, the most clinically relevant form of NHL. Although no proof yet exists of a role for these lesions in DLCL pathogenesis, the feature of the BCL-6 gene product, its specific pattern of expression in B cells, and the clustering of lesions disrupting its regulatory domain strongly suggest that deregulation of BCL-6 expression may contribute to DLCL development. A more precise definition of the role of BCL-6 in normal and neoplastic B-cell development is the goal of ongoing study of transgenic mice engineered either to express BCL-6 under heterologous promoters or lacking BCL-6 function due to targeted deletions. In addition to contributing to the understanding of DLCL pathogenesis, the identification of BCL-6 lesions may have relevant clinical implications. DLCL represent a heterogeneous group of neoplasms which are treated homogeneously despite the fact that only 50% of patients experience long-term disease-free survival (Schneider et al. 1990). The fact that BCL-6 rearrangements identify biologically and clinically distinct subsets of DLCL suggests that these lesions may be useful as markers in selection of differential therapeutic strategies based on different risk groups. Furthermore, the BCL-6 rearrangements can be used to identify and monitor the malignant clone with sensitive PCR-based techniques. Since clinical remission has been observed in a significant fraction of DLCL cases, these markers may serve as critical tools for sensitive monitoring of minimal residual disease and early diagnosis of relapse (Gribben et al. 1993).

Contraceptive social marketing is a way of supplying contraceptives to consumers who cannot afford to buy them at full market price, yet are not reached by the free public distribution program. The process involves supplying a subsidized product through existing commercial distribution networks, using the mass media and other retail marketing techniques to commercially advertise the products. India was the first country to introduce this concept to its family planning program. India's social marketing program is also the largest in the world. Over the past 25 years, total condom sales in India have expanded under the program from less than 10 million per year to more than one billion. The authors present an overview of India's social marketing initiative, describe the firms participating in the program, and summarize the lessons learned from the social marketing experience. Problems and prospects, and experiences and implications are discussed.