bluuebunny/crossref_metadata_2025 huggingface dataset:
Perforin-Mediated Cytotoxicity Is Critical for Surveillance of Spontaneous Lymphoma
Authors: Smyth Mark J. , Thia Kevin Y.T. , Street Shayna E.A. , MacGregor Duncan , Godfrey Dale I. , Trapani Joseph A.
Published: July 2002

Immune surveillance by cytotoxic lymphocytes against cancer has been postulated for decades, but direct evidence for the role of cytotoxic lymphocytes in protecting against spontaneous malignancy has been lacking. As the rejection of many experimental cancers by cytotoxic T lymphocytes and natural killer cells is dependent on the pore-forming protein perforin (pfp), we examined pfp-deficient mice for increased cancer susceptibility. Here we show that pfp-deficient mice have a high incidence of malignancy in distinct lymphoid cell lineages (T, B, NKT), indicating a specific requirement for pfp in protection against lymphomagenesis. The susceptibility to lymphoma was accentuated by simultaneous lack of expression of the p53 gene, mutations in which also commonly predispose to human malignancies, including lymphoma. In contrast, the incidence and age of onset of sarcoma was unaffected in p53-deficient mice. Pfp-deficient mice were at least 1,000-fold more susceptible to these lymphomas when transplanted, compared with immunocompetent mice in which tumor rejection was controlled by CD8+ T lymphocytes. This study is the first that implicates direct cytotoxicity by lymphocytes in regulating lymphomagenesis.
Germinal Center Initiation, Variable Gene Region Hypermutation, and Mutant B Cell Selection without Detectable Immune Complexes on Follicular Dendritic Cells
Authors: Hannum Lynn G. , Haberman Ann M. , Anderson Shannon M. , Shlomchik Mark J.
Published: July 2002

Serum antibody (Ab) can play several roles during B cell immune responses. Among these is to promote the deposition of immune complexes (ICs) on follicular dendritic cells (FDCs). ICs on FDCs are generally thought to be critical for normal germinal center (GC) formation and the development and selection of memory B cells. However, it has been very difficult to test these ideas. To determine directly whether FDC-bound complexes do indeed function in these roles, we have developed a transgenic (Tg) mouse in which all B lymphocytes produce only the membrane-bound form of immunoglobulin M. Immune Tg mice have 10,000-fold less specific Ab than wild-type mice and lack detectable ICs on FDCs. Nonetheless, primary immune responses and the GC reaction in these mice are robust, suggesting that ICs on FDCs do not play critical roles in immune response initiation and GC formation. Moreover, as indicated by the presence and pattern of somatic mutations, memory cell formation and selection appear normal in these IC-deficient GCs.
Nuclear Factor κb Is Required for the Development of Marginal Zone B Lymphocytes
Authors: Cariappa Annaiah , Liou Hsiou-Chi , Horwitz Bruce H. , Pillai Shiv
Published: July 2002

Although immunoglobulin (Ig)MhiIgDlo/−CD21hi marginal zone B cells represent a significant proportion of naive peripheral splenic B lymphocytes, few of the genes that regulate their development have been identified. This subset of peripheral B cells fails to emerge in mice that lack nuclear factor (NF)-κBp50. Less drastic reductions in marginal zone B cell numbers are also seen in the spleens of recombination activating gene (Rag)-2−/− mice reconstituted with NF-κBp65−/− fetal liver cells and in c-Rel−/− mice. In contrast, steady-state levels of IgDhi splenic follicular B cells are not significantly reduced in the absence of NF-κBp50, NF-κBp65, or c-Rel. Reconstitution of B cells in Rag-2−/− mice with a mixture of p50−/−/p65−/− fetal liver cells and Rag-2−/− bone marrow cells revealed that the generation of marginal zone B cells requires the expression of NF-κB in developing B cells, as opposed to supporting cells.
B Cell Development Is Arrested at the Immature B Cell Stage in Mice Carrying a Mutation in the Cytoplasmic Domain of Immunoglobulin β
Authors: Reichlin Amy , Hu Yun , Meffre Eric , Nagaoka Hitoshi , Gong Shiaoching , Kraus Manfred , Rajewsky Klaus , Nussenzweig Michel C.
Published: July 2002

The B cell receptor (BCR) regulates B cell development and function through immunoglobulin (Ig)α and Igβ, a pair of membrane-bound Ig superfamily proteins, each of which contains a single cytoplasmic immunoreceptor tyrosine activation motif (ITAM). To determine the function of Igβ, we produced mice that carry a deletion of the cytoplasmic domain of Igβ (IgβΔC mice) and compared them to mice that carry a similar mutation in Igα (MB1ΔC, herein referred to as IgαΔC mice). IgβΔC mice differ from IgαΔC mice in that they show little impairment in early B cell development and they produce immature B cells that respond normally to BCR cross-linking as determined by Ca2+ flux. However, IgβΔC B cells are arrested at the immature stage of B cell development in the bone marrow and die by apoptosis. We conclude that the cytoplasmic domain Igβ is required for B cell development beyond the immature B cell stage and that Igα and Igβ have distinct biologic activities in vivo.
Dynamic Tuning of T Cell Reactivity by Self-Peptide–Major Histocompatibility Complex Ligands
Authors: Wong Phillip , Barton Gregory M. , Forbush Katherine A. , Rudensky Alexander Y.
Published: July 2002

Intrathymic self-peptide–major histocompatibility complex class II (MHC) molecules shape the T cell repertoire through positive and negative selection of immature CD4+CD8+ thymocytes. By analyzing the development of MHC class II–restricted T cell receptor (TCR) transgenic T cells under conditions in which the endogenous peptide repertoire is altered, we show that self-peptide–MHC complexes are also involved in setting T cell activation thresholds. This occurs through changes in the expression level of molecules on thymocytes that influence the sensitivity of TCR signaling. Our results suggest that the endogenous peptide repertoire modulates T cell responsiveness in the thymus in order to enforce tolerance to self-antigens.
Functional Cloning of Src-like Adapter Protein-2 (SLAP-2), a Novel Inhibitor of Antigen Receptor Signaling
Authors: Holland Sacha J. , Liao X. Charlene , Mendenhall Marcy K. , Zhou Xiulan , Pardo Jorge , Chu Peter , Spencer Collin , Fu Alan , Sheng Ning , Yu Peiwen , Pali Erlina , Nagin Anup , Shen Mary , Yu Simon , Chan Eva , Wu Xian , Li Connie , Woisetschlager Max , Aversa Gregorio , Kolbinger Frank , Bennett Mark K. , Molineaux Susan , Luo Ying , Payan Donald G. , Mancebo Helena S.Y. , Wu Jun
Published: July 2002

In an effort to identify novel therapeutic targets for autoimmunity and transplant rejection, we developed and performed a large-scale retroviral-based functional screen to select for proteins that inhibit antigen receptor-mediated activation of lymphocytes. In addition to known regulators of antigen receptor signaling, we identified a novel adaptor protein, SLAP-2 which shares 36% sequence similarity with the known Src-like adaptor protein, SLAP. Similar to SLAP, SLAP-2 is predominantly expressed in hematopoietic cells. Overexpression of SLAP-2 in B and T cell lines specifically impaired antigen receptor-mediated signaling events, including CD69 surface marker upregulation, nuclear factor of activated T cells (NFAT) promoter activation and calcium influx. Signaling induced by phorbol myristate acetate (PMA) and ionomycin was not significantly reduced, suggesting SLAP-2 functions proximally in the antigen receptor signaling cascade. The SLAP-2 protein contains an NH2-terminal myristoylation consensus sequence and SH3 and SH2 Src homology domains, but lacks a tyrosine kinase domain. In antigen receptor–stimulated cells, SLAP-2 associated with several tyrosine phosphorylated proteins, including the ubiquitin ligase Cbl. Deletion of the COOH terminus of SLAP-2 blocked function and abrogated its association with Cbl. Mutation of the putative myristoylation site of SLAP-2 compromised its inhibitory activity and impaired its localization to the membrane compartment. Our identification of the negative regulator SLAP-2 demonstrates that a retroviral-based screening strategy may be an efficient way to identify and characterize the function of key components of many signal transduction systems.
Rapid Acquisition of Tissue-specific Homing Phenotypes by CD4+ T Cells Activated in Cutaneous or Mucosal Lymphoid Tissues
Authors: Campbell Daniel J. , Butcher Eugene C.
Published: July 2002

Effector and memory T cells can be subdivided based on their ability to traffic through peripheral tissues such as inflamed skin and intestinal lamina propria, a property controlled by expression of ‘tissue-specific’ adhesion and chemoattractant receptors. However, little is known about the development of these selectively homing T cell subsets, and it is unclear whether activation in cutaneous versus intestinal lymphoid organs directly results in effector/memory T cells that differentially express adhesion and chemoattracant receptors targeting them to the corresponding nonlymphoid site. We define two murine CD4+ effector/memory T cell subsets that preferentially localize in cutaneous or intestinal lymphoid organs by their reciprocal expression of the adhesion molecules P-selectin ligand (P-lig) and α4β7, respectively. We show that within 2 d of systemic immunization CD4+ T cells activated in cutaneous lymph nodes upregulate P-lig, and downregulate α4β7, while those responding to antigen in intestinal lymph nodes selectively express high levels of α4β7 and acquire responsiveness to the intestinal chemokine thymus-expressed chemokine (TECK). Thus, during an immune response, local microenvironments within cutaneous and intestinal secondary lymphoid organs differentially direct T cell expression of these adhesion and chemoattractant receptors, targeting the resulting effector T cells to the inflamed skin or intestinal lamina propria.
A Serine Residue in ClC-3 Links Phosphorylation–Dephosphorylation to Chloride Channel Regulation by Cell Volume
Authors: Duan Dayue , Cowley Suzanne , Horowitz Burton , Hume Joseph R.
Published: July 2002

In many mammalian cells, ClC-3 volume-regulated chloride channels maintain a variety of normal cellular functions during osmotic perturbation. The molecular mechanisms of channel regulation by cell volume, however, are unknown. Since a number of recent studies point to the involvement of protein phosphorylation/dephosphorylation in the control of volume-regulated ionic transport systems, we studied the relationship between channel phosphorylation and volume regulation of ClC-3 channels using site-directed mutagenesis and patch-clamp techniques. In native cardiac cells and when overexpressed in NIH/3T3 cells, ClC-3 channels were opened by cell swelling or inhibition of endogenous PKC, but closed by PKC activation, phosphatase inhibition, or elevation of intracellular Ca2+. Site-specific mutational studies indicate that a serine residue (serine51) within a consensus PKC-phosphorylation site in the intracellular amino terminus of the ClC-3 channel protein represents an important volume sensor of the channel. These results provide direct molecular and pharmacological evidence indicating that channel phosphorylation/dephosphorylation plays a crucial role in the regulation of volume sensitivity of recombinant ClC-3 channels and their native counterpart, ICl.vol.
Gating by Cyclic Gmp and Voltage in the α Subunit of the Cyclic Gmp–Gated Channel from Rod Photoreceptors
Authors: Benndorf Klaus , Koopmann Rolf , Eismann Elisabeth , Kaupp U. Benjamin
Published: July 2002

Gating by cGMP and voltage of the α subunit of the cGMP-gated channel from rod photoreceptor was examined with a patch-clamp technique. The channels were expressed in Xenopus oocytes. At low [cGMP] (<20 μM), the current displayed strong outward rectification. At low and high (700 μM) [cGMP], the channel activity was dominated by only one conductance level. Therefore, the outward rectification at low [cGMP] results solely from an increase in the open probability, Po. Kinetic analysis of single-channel openings revealed two exponential distributions. At low [cGMP], the larger Po at positive voltages with respect to negative voltages is caused by an increased frequency of openings in both components of the open-time distribution. In macroscopic currents, depolarizing voltage steps, starting from −100 mV, generated a time-dependent current that increased with the step size (activation). At low [cGMP] (20 μM), the degree of activation was large and the time course was slow, whereas at saturating [cGMP] (7 mM) the respective changes were small and fast. The dose–response relation at −100 mV was shifted to the right and saturated at significantly lower Po values with respect to that at +100 mV (0.77 vs. 0.96). Po was determined as function of the [cGMP] (at +100 and −100 mV) and voltage (at 20, 70, and 700 μM, and 7 mM cGMP). Both relations could be fitted with an allosteric state model consisting of four independent cGMP-binding reactions and one voltage-dependent allosteric opening reaction. At saturating [cGMP] (7 mM), the activation time course was monoexponential, which allowed us to determine the individual rate constants for the allosteric reaction. For the rapid rate constants of cGMP binding and unbinding, lower limits are determined. It is concluded that an allosteric model consisting of four independent cGMP-binding reactions and one voltage-dependent allosteric reaction, describes the cGMP- and voltage-dependent gating of cGMP-gated channels adequately.
Hydrodynamic Simulations of Flares on Accretion Disks
Authors: Williams Glen , Malatesta Kerriann H.
Published: July 2002

We have constructed a hydrodynamic simulation of flares on the accretion disks of cataclysmic variable stars. In these flares the disk photosphere is heated by a beam of suprathermal electrons. The beam energy flux, beam duration, position in the accretion disk, and accretion disk temperature were varied in 20 flare simulations. All the flare simulations show that above a site of maximum heating the gas is blown upward from the disk. Below this point the gas is compressed and heated. A non-LTE radiative transfer program calculates the resulting continuous emission and Balmer line radiation from the flare. The temporal development of each flare model is followed by calculating the radiation at 15–20 time steps. The Hβ line flux from accretion disks is estimated for 20 dwarf novae and 12 nova and nova-like systems by using information gathered from the literature. We then use a simple approximation for the rate of flaring across an accretion disk to see whether flares can account for all the Hβ emission. The rate of flickering observed in cataclysmic variables is used as a constraint on this model. Using flickering rates from one study we find that if each observed flicker is one magnetic flare, then flares can account for only 1%–2% of the Hβ emission. A much higher flare rate can account for the observed Hβ emission if flickering studies underestimate the true rate of flaring. A flare avalanche model may account for both the observed Hβ flux and the observed flickering.
Is it appropriate to use structured abstracts in social science journals?
Authors: Hartley James
Published: July 2002

BACKGROUND

Structured abstracts (which use sub‐headings like this one) have now become widespread in medical research journals.

AIM

The aim of this paper is to consider whether or not such structured abstracts can be used effectively in social science journals.

METHOD

The paper reviews a selection of studies of carried out by the author and his colleagues to see if structured abstracts written for social science journals are more informative, easier to read, and easier to search than are their traditional equivalents.

RESULTS

The results suggest that structured abstracts do, indeed, have these virtues, and that they are thus appropriate for social science journals.

CONCLUSION

The author therefore recommends that the editors of social science journals consider adopting structured abstracts.
Elastic electron scattering and vibrational excitation of CO2in the threshold energy region
Authors: K -H Kochem  , W Sohn  , N Hebel  , K Jung  , H Ehrhardt
Published: July 2002

In a crossed-beam experiment e-+CO2elastic scattering and the excitation of the three fundamental vibrational modes have been investigated in the energy region below the2Piushape resonance. Angular and energy dependences of the differential cross sections have been determined in absolute units below 1.05 eV collision energy. For elastic scattering the large increase of the cross section towards zero energy is consistent with the existence of a virtual state. The angular dependences of the elastic differential cross sections below 1 eV indicate that direct scattering is important even at very low collision energies. The excitation of the two infrared-active modes (010) and (001) below 1 eV is mainly determined by the direct excitation via the dipole potential, whereas the excitation of the symmetric-stretch mode (100) is dominated by s-wave scattering. A comparison with recent theoretical investigations shows that angular and energy dependences for this mode near threshold are strongly influenced by the virtual state of the e-+CO2potential.
An application of the polarized-orbital approximation to electron impact excitation of atomic hydrogen
Authors: M D Lloyd  , M R C McDowell
Published: July 2002

Two approximations for electron impact excitation of atomic hydrogen are discussed. Both include polarization effects to first order. In the first (A) a polarized Born approximation, the unperturbed ground-state target eigenfunction is replaced in the direct term of the scattering amplitude by a perturbed first-order function. The second approximation treated (B) consists of replacing the incident plane wave appropriate to Born's approximation by polarized orbitals for the incident electron. Calculations are carried out in both models, for the 1s -> 2s and 1s -> 2p transitions. In all cases the calculated cross sections lie below the corresponding Born approximation and approach it at high impact energies. In the case of approximation (B), when non-adiabatic effects are included in determining the polarized orbitals, the calculated cross sections are in good agreement with experiment near threshold (but do not give the detailed resonance structure).
Extension of the C2 (A 3πg-X ′ 3πu) band system
Authors: K S Kini  , M I Savadatti
Published: July 2002

New bands from v′ up to 14, belonging to the A 3IIg-X′ 3IIu transition of C2, observed in the spectra of a discharge through a flowing mixture of benzene and argon, are reported.
Accessory for specular reflectance measurements with double-beam spectrophotometers
Authors: G Cappuccio  , S D'Angelo
Published: July 2002

With the apparatus described, specular reflectance measurements may be made on small sample areas at near-normal incidence, thereby minimising polarisation effects. For each beam of the spectrophotometer, only two optical elements are required: a spherical mirror and a removable reflecting prism. This facilitates rapid change-over between transmission and reflection measurements and permits an easy visual check of the alignment of the accessory. The simple light paths involved and the maintenance of the original beam convergence keep asymmetries to a minimum and increase the reliability of the results.
Dead time circuit (radiation measurement)
Authors: S Takeuchi  , T Naito
Published: July 2002

A monostable multivibrator suitable for use as a dead time simulator to be inserted in radiation measuring systems is presented. It features very fast recovery characteristics.
A high-voltage solid state current divertor for use with AC electric strength test circuits
Authors: M Kando
Published: July 2002

The circuit of a high-voltage solid state current divertor is described and its effectiveness in reducing damage to the electrodes in a test cell demonstrated.
The use of different input signals for dynamic characterisation in isothermal microcalorimetry
Authors: O Lopez-Mayorga  , P L Mateo  , M Cortijo
Published: July 2002

Some specific advantages, such as the saving of both time and materials, are to be gained from carrying out measurements under dynamic conditions with instruments that are normally used for steady-state experiments. To do this, however, it is necessary first of all to determine the dynamic characteristics of the system. Thus, the dynamic characterisation of an LKB flow microcalorimeter has been achieved by studying its transfer function. For this an analysis of the response to three different kinds of input signal, a power impulse, a power step and a periodic power function, was used. A non-linear least-squares method was applied in the calculation of the time constants in the case of the frequency analysis of the response to a periodic power input. Several time constants ranging from 0.5 to 70 s were thus obtained from the output response.
The technology of diamond anvil high-pressure cells: II. Operation and use
Authors: I L Spain  , D J Dunstan
Published: July 2002

For pt.I see ibid., vol.22, no.11, p.913-23, Nov. 1989. The operation and use of diamond anvil cells is discussed. Experimental details pertaining to the assembly of cells preparation of gaskets, compressing media, sample preparation and handling, pressure measurement and types of spectroscopic and electrical measurement which can be carried out are given.
Instrumental and analysis improvements in multifrequency phase fluorometry
Authors: K Clays  , J Jannes  , Y Engelborghs  , A Persoons
Published: July 2002

High-precision resolution for multi-exponential fluorescence decay is obtained by completely automated multifrequency phase fluorometry, using the harmonic content of the pulse train of a stabilised, mode-locked, cavity-dumped dye laser. The principle of this method has been described previously (Lackowicz et al. 1986). By stabilising the pump laser, the frequency stability of the cross correlation product was considerably enhanced. The use of a flat-top band-pass filter enables fast measurement and ensures high phase stability. Phase shifts with a standard deviation of 0.1 degree are measured at the harmonics of the basic frequency (400 kHz) with a digital counter. All instruments, including monochromator and cell exchanger, are fully computer-controlled. The instrument has been used successfully to elucidate the complex fluorescence decay of proteins, antibiotics and some inorganic Cu complexes.
An improved iteration method for calculating the axial potential distribution in slit-aperture electrostatic lenses
Authors: M J Wallington
Published: July 2002

Axial potential distributions in electrostatic slit-aperture lenses, consisting of plane and parallel electrodes, are derived using the method of conformal transformation. An improved iterative scheme is given which, for the first time, enables solutions to be obtained for multi-electrode configurations in which the aperture widths are larger than the electrode separations. No special conditions relating one aperture width to another, or relating one electrode spacing to another, were assumed. As an example, the axial potential distribution in the electron bombardment source used in AEI mass spectrometers was calculated; for this an analogue consisting of five apertured planes and an apertureless plane was used. Electrodes of finite thickness were each represented by two planes of infinitesimal thickness. The same problem required computer time greater by at least a factor of ten when solved by the method of numerical relaxation.
A reliable temperature cell housing for pulse radiolysis flow systems
Authors: P Wardman
Published: July 2002

A cell housing is described which allows the convenient variation in temperature between -160 and +150 degrees C of liquid samples in a spectroscopic cell which may be made part of a flow system to permit sample changing.
A plunger viscometer with digital readout
Authors: J Cochrane  , G Harrison
Published: July 2002

A description is given of a plunger viscometer which can be used to measure viscosities in the range 0.2kP to 1 MP with an accuracy of +or-1.5%. The viscometer consists of a plunger which is forced into a barrel containing the liquid sample by the action of a known mass. A ball-bearing bush is used to eliminate frictional effects from the system supporting the mass. The motion of the plunger is measured optically using a diffraction grating, and a digital measuring system is arranged to display the viscosity of the sample directly. The time necessary to take a measurement is in the range 20-1000 s. Typical sets of results are shown and a comparison is made with results obtained using suspended level capillary viscometers.
RF biasing through capacitive collector to target coupling in RF diode sputtering
Authors: O Christensen  , P Jensen
Published: July 2002

An RF sputtering system which is suitable for deposition of both conductive and nonconductive thin films by bias sputtering is described. The substrate bias is obtained by capacitive collector to target coupling, the capacitance of the collector dark space and an external capacitor being used for voltage division. The influence of target voltage and sputtering pressure on bias generation is considered. When using RF discharge no electrode is in direct electric contact with the plasma, and a systematic error is introduced by measuring the bias voltage as collector DC voltage relative to the target's earthed counter electrode, which error is discussed. Data are presented on the temperature coefficient of resistance in bias-sputtered nickel films showing similar dependence on target voltage and on bias voltage.
A press for the infrared spectroscopic examination of air sensitive compounds
Authors: D A Symon  , J McClurg
Published: July 2002

Describes design of a press for the preparation of air sensitive materials for examination by infrared spectroscopy. The materials can be dispersed in a matrix of alkali metal halide or polythene. The design allows preparation of the pressed disc to be carried out in a controlled environment, for example inert atmosphere such as dry nitrogen, without the use of hydraulic presses.
An expensive digital method for the measurement of isotopic ratios
Authors: A de Sa  , J G Mitchell
Published: July 2002

For isotope analysis the versatility of integrating type digital voltmeters is unnecessary. An inexpensive method of constructing a device which meets all the essential requirements, at a cost which is a fraction of that of commercially available instruments, is described. The device is easily constructed from integrated circuits and has a linearity of response of one part in 104. A five digit display and a binary coded decimal (BCD) output are available simultaneously.
Magnetic monitors for in-pile measurements of maximum temperature in irradiated samples
Authors: D Stoelzl  , R Sizmann
Published: July 2002

Magnetic probes are described for monitoring the maximum temperatures in samples irradiated in nuclear reactors. The specifications of the probes are: small size (25 mm*1.5 mm wires), easy reading, dependable temperature indication to within a few degrees. The measuring range extends in principle from room temperature up to 1100 degrees C. The reliability of the method is illustrated with in-pile measurements utilizing Ni-18.7 at.% Cu probes which cover the important range from room temperature to 130 degrees C.
A square root circuit to linearize feedback in temperature controllers
Authors: D T Smith
Published: July 2002

A circuit is described which gives an output
voltage proportional to the square root of the input. This
has proved useful in feedback temperature controllers to
make the power developed in a resistive heater proportional
to the feedback signal, and so give a loop gain independent
of temperature error.
A remote pollution monitor
Authors: J W Haslett  , J J Havlena
Published: July 2002

A method for continuously monitoring a city-wide pollution cloud using optical techniques is described. An automatic rotating polarizing filter is used in conjunction with a commercially available time-lapse camera to provide maximum image contrast under all ambient light conditions. The circuitry used to actuate the polarizing filter is described in detail.
A simple neutron guide tube and diffractometer for small-angle scattering of cold neutrons
Authors: B C G Haywood  , D L Worcester
Published: July 2002

A neutron guide tube and diffractometer for measurements of small- angle Bragg diffraction are described. Application to studies of biological structures is demonstrated by preliminary diffraction data from the membranes of the myelin sheath of dog sciatic nerve.
On upper bounds of Chalk and Hua for exponential sums
Authors: Cochrane Todd , Zheng Zhiyong
Published: July 2002

Let

f
f

be a polynomial of degree

d
d

with integer coefficients,

p
p

any prime,

m
m

any positive integer and

S
(
f
,

p
m

)

S(f,p^m)

the exponential sum
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="upper S left-parenthesis f comma p Superscript m Baseline right-parenthesis equals sigma-summation Underscript x equals 1 Overscript p Superscript m Baseline Endscripts e Subscript p Sub Superscript m Baseline left-parenthesis f left-parenthesis x right-parenthesis right-parenthesis">

S
(
f
,

p
m

)
=

∑

x
=
1

p
m

e

p
m

(
f
(
x
)
)

S(f,p^m)= \sum _{x=1}^{p^m} e_{p^m}(f(x))

. We establish that if

f
f

is nonconstant when read

(
mod

p
)

\pmod p

, then

|

S
(
f
,

p
m

)

|

≤
4.41

p

m
(
1
−

1
d

)

|S(f,p^m)|\le 4.41 p^{m(1-\frac 1d)}

. Let

t
=

ord
p

(

f
′

)

t=\text {ord}_p(f’)

, let

α
\alpha

be a zero of the congruence

p

−
t

f
′

(
x
)
≡
0

(
mod

p
)

p^{-t}f’(x) \equiv 0 \pmod p

of multiplicity

ν
\nu

and let

S
α

(
f
,

p
m

)

S_\alpha (f,p^m)

be the sum

S
(
f
,

p
m

)

S(f,p^m)

with

x
x

restricted to values congruent to

α

(
mod

p
m

)

\alpha \pmod {p^m}

. We obtain
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="StartAbsoluteValue upper S Subscript alpha Baseline left-parenthesis f comma p Superscript m Baseline right-parenthesis EndAbsoluteValue less-than-or-equal-to min left-brace right-brace comma nu comma 3.06 p Superscript StartFraction t Over nu plus 1 EndFraction Baseline p Superscript m left-parenthesis 1 minus StartFraction 1 Over nu plus 1 EndFraction right-parenthesis">

|

S
α

(
f
,

p
m

)

|

≤
min
{
ν
,
3.06
}

p

t

ν
+
1

p

m
(
1
−

1

ν
+
1

)

|S_\alpha (f,p^m)| \le \min \{\nu ,3.06\} p^{\frac t{\nu +1}}p^{m(1-\frac 1{\nu +1})}

for

p
p

odd,

m
≥
t
+
2

m \ge t+2

and

d
p

(
f
)
≥
1

d_p(f)\ge 1

. If, in addition,

p
≥
(
d
−
1

)

(
2
d
)

/

(
d
−
2
)

p \ge (d-1)^{(2d)/(d-2)}

, then we obtain the sharp upper bound
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="StartAbsoluteValue upper S Subscript alpha Baseline left-parenthesis f comma p Superscript m Baseline right-parenthesis EndAbsoluteValue less-than-or-equal-to p Superscript m left-parenthesis 1 minus StartFraction 1 Over nu plus 1 EndFraction right-parenthesis">

|

S
α

(
f
,

p
m

)

|

≤

p

m
(
1
−

1

ν
+
1

)

|S_\alpha (f,p^m)| \le p^{m(1-\frac 1{\nu +1})}

.
A new uncountably categorical group
Authors: Baudisch Andreas
Published: July 2002

We construct an uncountably categorical group with a geometry that is not locally modular. It is not possible to interpret a field in this group. We show the group is CM-trivial.
Multiplicative 𝜂-quotients
Authors: Martin Yves
Published: July 2002

Let

η
(
z
)

\eta (z)

be the Dedekind

η
\eta

-function. In this work we exhibit all modular forms of integral weight
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="f left-parenthesis z right-parenthesis equals eta left-parenthesis t 1 z right-parenthesis Superscript r 1 Baseline eta left-parenthesis t 2 z right-parenthesis Superscript r 2 Baseline ellipsis eta left-parenthesis t Subscript s Baseline z right-parenthesis Superscript r Super Subscript s">

f
(
z
)
=
η
(

t
1

z

)

r
1

η
(

t
2

z

)

r
2

…
η
(

t
s

z

)

r
s

f(z) = \eta (t_1z)^{r_1}\eta (t_2z)^{r_2}\dots \eta (t_sz)^{r_s}

, for positive integers

s
s

and

t
j

t_j

and arbitrary integers

r
j

r_j

, such that both

f
(
z
)

f(z)

and its image under the Fricke involution are eigenforms of all Hecke operators. We also relate most of these modular forms with the Conway group

2

C
o

1

2 \mathrm {Co}_1

via a generalized McKay-Thompson series.
Stabilized wavelet approximations of the Stokes problem
Authors: Canuto Claudio , Masson Roland
Published: July 2002

We propose a new consistent, residual-based stabilization of the Stokes problem. The stabilizing term involves a pseudo-differential operator, defined via a wavelet expansion of the test pressures. This yields control on the full

L
2

L^2

-norm of the resulting approximate pressure independently of any discretization parameter. The method is particularly well suited for being applied within an adaptive discretization strategy. We detail the realization of the stabilizing term through biorthogonal spline wavelets, and we provide some numerical results.
New maximal prime gaps and first occurrences
Authors: Nicely Thomas
Published: July 2002

The search for first occurrences of prime gaps and maximal prime gaps is extended to

10

15

10^{15}

. New maximal prime gaps of 806 and 906 are found, and sixty-two previously unpublished first occurrences are found for gaps varying from 676 to 906.
Nonexistence conditions of a solution for the congruence 𝑥₁^{𝑘}+⋯+𝑥_{𝑠}^{𝑘}≡𝑁(\mod𝑝ⁿ)
Authors: Sekigawa Hiroshi , Koyama Kenji
Published: July 2002

We obtain nonexistence conditions of a solution for of the congruence

x
1
k

+
⋯
+

x
s
k

≡
N

(
mod

p
n

)

x_1^k+\cdots +x_s^k\equiv N\pmod {p^n}

, where

k
≥
2

k\geq 2

,

s
≥
2

s\geq 2

and

N
N

are integers, and

p
n

p^n

is a prime power. We give nonexistence conditions of the form

(
s
,
N
mod

p
n

)

(s, N\bmod {p^n})

for

k
=
2

k=2

,

3
3

,

4
4

,

5
5

,

7
7

, and of the form

(
s
,

p
n

)

(s, p^n)

for

k
=
11

k=11

,

13
13

,

17
17

,

19
19

. Furthermore, we complete some tables concerned with Waring’s problem in

p
p

-adic fields that were computed by Hardy and Littlewood.
Deletion Mutants in COP9/Signalosome Subunits in Fission YeastSchizosaccharomyces pombeDisplay Distinct Phenotypes
Authors: Mundt Kirsten E. , Liu Cong , Carr Antony M.
Published: July 2002

The COP9/signalosome complex is highly conserved in evolution and possesses significant structural similarity to the 19S regulatory lid complex of the proteasome. It also shares limited similarity to the translation initiation factor eIF3. The signalosome interacts with multiple cullins in mammalian cells. In the fission yeastSchizosaccharomyces pombe, the Csn1 subunit is required for the removal of covalently attached Nedd8 from Pcu1, one of threeS. pombe cullins. It remains unclear whether this activity is required for all the functions ascribed to the signalosome. We previously identified Csn1 and Csn2 as signalosome subunits inS. pombe. csn1 and csn2 null mutants are DNA damage sensitive and exhibit slow DNA replication. Two further putative subunits, Csn4 and Csn5, were identified from the S. pombe genome database. Herein, we characterize null mutations of csn4 and csn5 and demonstrate that both genes are required for removal of Nedd8 from the S. pombe cullin Pcu1 and that their protein products associate with Csn1 and Csn2. However, neither csn4 norcsn5 null mutants share the csn1 andcsn2 mutant phenotypes. Our data suggest that the subunits of the signalosome cannot be considered as a distinct functional unit and imply that different subunits of the signalosome mediate distinct functions.
Clustering of Procoagulation, Inflammation, and Fibrinolysis Variables with Metabolic Factors in Insulin Resistance Syndrome
Authors: Sakkinen Pamela A. , Wahl Patricia , Cushman Mary , Lewis Michael R. , Tracy Russell P.
Published: July 2002

The known metabolic cardiovascular disease risk factors associated with insulin resistance syndrome (IRS) do not adequately explain the excess cardiovascular disease risk attributed to this syndrome, and abnormalities in hemostatic variables may contribute to this excess risk. Using data from 322 nondiabetic elderly men and women (aged 65–100 years) participating in the Cardiovascular Health Study during 1989–1990, the authors performed factor analysis on 10 metabolic risk factors associated with IRS and 11 procoagulation, inflammation, and fibrinolysis variables to examine the clustering of the metabolic and hemostatic risk markers. Factor analysis of the metabolic variables confirmed four uncorrelated factors: body mass, insulin/glucose, lipids, and blood pressure. Adding the hemostatic variables yielded three new factors interpreted as inflammation, vitamin K-dependent proteins, and procoagulant activity. Plasminogen activator inhibitor-1 clustered with the body mass factor, supporting the hypothesis that obesity is related to impaired fibrinolysis. Fibrinogen clustered with the inflammation summary factor rather than procoagulant activity, supporting the position that fibrinogen principally reflects underlying inflammation rather than procoagulant potential. The authors conclude that should hemostatic variables be shown to contribute to IRS-related cardiovascular disease, apart from plasminogen activator inhibitor-1, they may do so independently of the established metabolic abnormalities. Am J Epidemiol 2000;152:897–907.
Genes regulated cooperatively by one or more transcription factors and their identification in whole eukaryotic genomes.
Authors: Wagner A
Published: July 2002

MOTIVATION: The question addressed here is how cooperative interactions among transcription factors (TFs), a very frequent phenomenon in eukaryotic transcriptional regulation, can be used to identify genes that are regulated by one or more TFs with known DNA binding specificities. Cooperativity may be homotypic, involving binding of only one transcription factor to multiple sites in a gene's regulatory region. It may also be heterotypic, involving binding of more than one TF. Both types of cooperativity have in common that the binding sites for the respective TFs form tightly linked 'clusters', groups of binding sites often more closely associated than expected by chance alone. RESULTS: A statistical technique suitable for the identification of statistically significant homotypic or heterotypic TF binding site clusters in whole eukaryotic genomes is presented. It can be used to identify genes likely to be regulated by the TFs. Application of the technique is illustrated with two transcription factors involved in the cell cycle and mating control of the yeast Saccharomyces cerevisiae, indicating that the results obtained are biologically meaningful. This rapid and inexpensive computational method of generating hypotheses about gene regulation thus generates information that may be used to guide subsequent costly and laborious experimental approaches, and that may aid in the assignment of biological functions to putative open reading frames.
Functional promoter modules can be detected by formal models independent of overall nucleotide sequence similarity.
Authors: Klingenhoff A , Frech K , Quandt K , Werner T
Published: July 2002

MOTIVATION: Gene regulation often depends on functional modules which feature a detectable internal organization. Overall sequence similarity of these modules is often insufficient for detection by general search methods like FASTA or even Gapped BLAST. However, it is of interest to evaluate whether modules, often known from experimental analysis of single sequences, are present in other regulatory sequences. RESULTS: We developed a new method (FastM) which combines a search algorithm for individual transcription factor binding sites (MatInspector) with a distance correlation function. FastM allows fast definition of a model of correlated binding sites derived from as little as a single promoter or enhancer. ModelInspector results are suitable for evaluation of the significance of the model. We used FastM to define a model for the experimentally verified NFkappaB/IRF1 regulatory module from the major histocompatibility complex (MHC) class I HLA-B gene promoter. Analysis of a test set of sequences as well as database searches with this model showed excellent correlation of the model with the biological function of the module. These results could not be obtained by searches using FASTA or Gapped BLAST, which are based on sequence similarity. We were also able to demonstrate association of a hypothetical GRE-GRE module with viral sequences based on analysis of several GenBank sections with this module. AVAILABILITY: The WWW version of FastM is accessible at: http://www.gsf.de/cgi-bin/fastm. pl and http://genomatix.gsf.de/cgi-bin/fastm2/fastm.pl
The Biopolymer Markup Language.
Authors: Feny√∂ D
Published: July 2002

SUMMARY: An XML derived from a data model designed to be a hierarchical representation of an organism has been specified and a browser to use this language has been developed. AVAILABILITY: The language definition is available in HTML form at http://www.proteometrics.com/BIOML/. The BioML browser is available on request from the author.
Sequence analysis by additive scales: DNA structure for
sequences and repeats of all lengths
Authors: Baldi Pierre , Baisnée Pierre-François
Published: July 2002

Motivation: DNA structure plays an important role in a variety of biological processes. Different di- and tri-nucleotide scales have been proposed to capture various aspects of DNA structure including base stacking energy, propeller twist angle, protein deformability, bendability, and position preference. Yet, a general framework for the computational analysis and prediction of DNA structure is still lacking. Such a framework should in particular address the following issues: (1) construction of sequences with extremal properties; (2) quantitative evaluation of sequences with respect to a given genomic background; (3) automatic extraction of extremal sequences and profiles from genomic databases; (4) distribution and asymptotic behavior as the length Nof the sequences increases; and (5) complete analysis of correlations between scales.

Results: We develop a general framework for sequence analysis based on additive scales, structural or other, that addresses all these issues. We show how to construct extremal sequences and calibrate scores for automatic genomic and database extraction. We show that distributions rapidly converge to normality as Nincreases. Pairwise correlations between scales depend both on background distribution and sequence length and rapidly converge to an analytically predictable asymptotic value. For di- and tri-nucleotide scales, normal behavior and asymptotic correlation values are attained over a characteristic window length of about 10–15 bp. With a uniform background distribution, pairwise correlations between empirically-derived scales remain relatively small and roughly constant at all lengths, except for propeller twist and protein deformability which are positively correlated. There is a positive (resp. negative) correlation between dinucleotide base stacking (resp. propeller twist and protein deformability) and AT-content that increases in magnitude with length. The framework is applied to the analysis of various DNA tandem repeats. We derive exact expressions for counting the number of repeat unit classes at all lengths. Tandem repeats are likely to result from a variety of different mechanisms, a fraction of which is likely to depend on profiles characterized by extreme structural features.

Contact: pfbaldi@ics.uci.edu; baisnee@ics.uci.edu

To whom all correspondence should be addressed.
Processing and quality control of DNA array hybridization data
Authors: Beißbarth T. , Fellenberg K. , Brors B. , Arribas-Prat R. , Boer J. M. , Hauser N. C. , Scheideler M. , Hoheisel J. D. , Schütz G. , Poustka A. , Vingron M.
Published: July 2002

Motivation: The technology of hybridization to DNA arrays is used to obtain the expression levels of many different genes simultaneously. It enables searching for genes that are expressed specifically under certain conditions. However, the technology produces large amounts of data demanding computational methods for their analysis. It is necessary to find ways to compare data from different experiments and to consider the quality and reproducibility of the data.

Results: Data analyzed in this paper have been generated by hybridization of radioactively labeled targets to DNA arrays spotted on nylon membranes. We introduce methods to compare the intensity values of several hybridization experiments. This is essential to find differentially expressed genes or to do pattern analysis. We also discuss possibilities for quality control of the acquired data.

Availability: http://www.dkfz.de/tbi

Contact: M.Vingron@dkfz-heidelberg.de

To whom correspondence should be addressed.
PHAT: a transmembrane-specific substitution matrix
Authors: Ng Pauline C. , Henikoff Jorja G. , Henikoff Steven
Published: July 2002

Motivation: Database searching algorithms for proteins use scoring matrices based on average protein properties, and thus are dominated by globular proteins. However, since transmembrane regions of a protein are in a distinctly different environment than globular proteins, one would expect generalized substitution matrices to be inappropriate for transmembrane regions.

Results: We present the PHAT (predicted hydrophobic and transmembrane) matrix, which significantly outperforms generalized matrices and a previously published transmembrane matrix in searches with transmembrane queries. We conclude that a better matrix can be constructed by using background frequencies characteristic of the twilight zone, where low-scoring true positives have scores indistinguishable from high-scoring false positives, rather than the amino acid frequencies of the database. The PHAT matrix may help improve the accuracy of sequence alignments and evolutionary trees of membrane proteins.

Availability: http://www.blocks.fhcrc.org/~pauline

Contact: steveh@muller.fhcrc.org

To whom correspondence should be addressed.
XML, bioinformatics and data integration
Authors: Achard Frédéric , Vaysseix Guy , Barillot Emmanuel
Published: July 2002

Motivation: The eXtensible Markup Language (XML) is an emerging standard for structuring documents, notably for the World Wide Web. In this paper, the authors present XML and examine its use as a data language for bioinformatics. In particular, XML is compared to other languages, and some of the potential uses of XML in bioinformatics applications are presented. The authors propose to adopt XML for data interchange between databases and other sources of data. Finally the discussion is illustrated by a test case of a pedigree data model in XML.

Contact: Emmanuel.Barillot@infobiogen.fr

* To whom correspondence should be addressed.

3 Present address: Cereon Genomics, 45 Sidney St, Cambridge, MA 02139, USA.
Distribution of genes for lysine biosynthesis through the

aminoadipate pathway among prokaryotic genomes
Authors: Nishida Hiromi
Published: July 2002

Summary: Deinococcus radioduranshas homologous genes to the genes which from the Thermus thermophilus gene cluster for lysine biosynthesis. Interestingly, those genes are clustered in Thermus, nevertheless they are scattered in Deinococcus. A similar gene cluster has only been found in Pyrococcus. However, the phylogenetic analyses indicated that the deduced gene products from Deinococcus were the most closely related to the proteins encoded in the Thermus gene cluster for lysine biosynthesis. Therefore, those genes had not been transferred horizontally between Pyrococcus and Thermus. It is strongly suggested that a common ancestor of Deinococcus and Thermus possessed the genes for lysine biosynthesis through the aminoadipate pathway. These had been clustered through the evolution of Thermus or had been scattered from the gene cluster through the evolution of Deinococcus. In addition, I showed that LysW and its homologues were specialized proteins for the prokaryotic lysine biosynthesis through the aminoadipate pathway.

Contact: hnishida@iam.u-tokyo.ac.jp